The Role of miRNAs as Therapeutic Tools in Sickle Cell Disease

Background and Objectives: Sickle cell disorder (SCD) is a paradigmatic example of a complex monogenic disorder. SCD is characterized by the production of abnormal hemoglobin, primarily in the deoxygenated state, which makes erythrocytes susceptible to intracellular hemoglobin polymerization. Functional studies have affirmed that the dysregulation of miRNAs enhances clinical severity or has an ameliorating effect in SCD. miRNAs can be effectively regulated to reduce the pace of cell cycle progression, to reduce iron levels, to influence hemolysis and oxidative stress, and most importantly, to increase γ-globin gene expression and enhance the effectiveness of hydroxyurea. Results: This review highlights the roles played by some key miRNAs in hemoglobinopathies, especially in hematopoiesis, erythroid differentiation, and severity of anemia, which make miRNAs attractive molecular tools for innovative therapeutic approaches. Conclusion: In this era of targeted medicine, miRNAs mimics and antagomirs may be promising inducers of HbF synthesis which could ameliorate the clinical severity of SCD.

Deciphering Genetic Alterations of Taiwanese Pancreatic Adenocarcinoma With Targeted Sequencing

Purpose Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related death in Taiwan, and its incidence is increasing. The development of PAC involves successive accumulation of multiple genetic alternations. Understanding the molecular pathogenesis and heterogeneity of PAC may facilitate personalized treatment for PAC and identify therapeutic agents.Materials and Methods We performed next-generation sequencing (NGS) with targeted panels to explore the molecular changes underlying PAC in Taiwan. The Ion Torrent Oncomine Comprehensive Panel (OCP) was used for PAC metastatic lesions, and more PAC samples were sequenced with the Ion AmpliSeq Cancer Hot Spot (CHP) v2 panel.ResultsFive fresh-frozen paraffin-embedded (FFPE) specimens were successfully assayed with the OCP, and KRAS was the most prevalent alternation, which might contraindicate the use of anti-EGFR therapy. One PAC patient harbored a FGFR2 p.C382R mutation, who might derive benefit from FGFR tyrosine kinase inhibitor. Additional 38 samples assayed with CHP v2 showed 113 hotspot variants, corresponding to 54 COSMID IDs. The most frequently mutated genes were TP53, KRAS, HRAS, and PDGFRA, (29, 23, 14, 10 hotspot variants), impacting 11, 23, 14, and 10 PAC patients. Highly pathogenic variants including COSM22413 (PDGFRA, FATHMM predicted score: 0.88), COSM520, COSM521, COSM518 (KRAS, FATHMM predicted score: 0.98) were reported.ConclusionsBy using NGS with targeted panel, somatic mutations with therapeutic potential were identified. The combination of clinical and genetic information is useful for decision making and precise selection of targeted medicine.

Scalable analysis of multi-modal biomedical data

Background Targeted diagnosis and treatment options are dependent on insights drawn from multi-modal analysis of large-scale biomedical datasets. Advances in genomics sequencing, image processing, and medical data management have supported data collection and management within medical institutions. These efforts have produced large-scale datasets and have enabled integrative analyses that provide a more thorough look of the impact of a disease on the underlying system. The integration of large-scale biomedical data commonly involves several complex data transformation steps, such as combining datasets to build feature vectors for learning analysis. Thus, scalable data integration solutions play a key role in the future of targeted medicine. Though large-scale data processing frameworks have shown promising performance for many domains, they fail to support scalable processing of complex datatypes. Solution To address these issues and achieve scalable processing of multi-modal biomedical data, we present TraNCE, a framework that automates the difficulties of designing distributed analyses with complex biomedical data types. Performance We outline research and clinical applications for the platform, including data integration support for building feature sets for classification. We show that the system is capable of outperforming the common alternative, based on “flattening” complex data structures, and runs efficiently when alternative approaches are unable to perform at all.

Gene therapy vectors for targeting the heart

The delivery of therapeutic drugs to the heart continues to be a challenge. Developing precise strategies to target the heart is equally as important as discovering new therapeutic medications. To grow this sector, a program that focuses on targeted delivery to the heart, as well as efforts to improve cardiac selectivity and retention of therapeutic medications, may be required. Targeted medicine distribution is one of the most important and unresolved issues in pharmacology. Viruses, on the other hand, have evolved unique and extremely accurate tropisms toward their biological targets through the usage of specific binding proteins. The inclusion of these viral proteins into the plasma membrane of EVs should improve the efficiency with which EVs transport drugs to target cells. Understanding the structure, content, and mechanisms of exosome–cell interactions and uptake might also help with the creation of bioengineered exosomes and other EVs that might be used as targeted drug delivery vehicles. In addition to establishing the optimal vector for each therapeutic ingredient, effective clinical translation of cardiac medicines requires minimally invasive yet highly selective delivery techniques.

Review of novel tissue-based biomarkers for prostate cancer: towards personalised and targeted medicine

Background: Prostate cancer is the most commonly diagnosed cancer in men and responsible for about 10% of all cancer mortality in both Canadian and American men. Currently, serum PSA level is the most commonly used test for the detection of prostate cancer, though the levels can also be elevated in benign conditions, has limited specificity and has a high rate of overdiagnosis and treatment of indolent disease. Consequently, in recent years, several investigations have been conducted to identify novel cancer biomarkers capable of both effective screening and diagnosis, as well as assisting to shift the diagnostic and treatment paradigm of prostate cancer towards more patient-specific and targeted medicine. The goal of this narrative review paper is to describe eleven novel and promising tissue-based biomarkers for prostate cancer capable to account for individual patient variabilities and have the potential for risk assessment, early detection and diagnosis, identification of patients who will benefit from a particular treatment and monitoring patient response to treatment. Materials and methods: We searched several databases from August to December 2020 for relevant studies published in English between 2000 and 2020 and reporting on tissue-based biomarkers for screening and early diagnosis, treatment and monitoring of prostate cancer. Conclusions: Emerging prostate cancer biomarkers have the potential to guide clinical decision-making since they have the potential to detect the disease early, measure the risk of developing the disease and the risk of progression, provide accurate information of patient response to a specific treatment and are capable of informing clinicians about the likely outcome of a cancer diagnosis independent of the treatment received. Therefore, the future holds promise for personalised and targeted medicine from prevention to diagnosis and treatment that considers the individual patient’s variabilities in the management of prostate cancer.

Review of novel liquid-based biomarkers for prostate cancer: towards personalised and targeted medicine

Background: Prostate cancer is the most commonly diagnosed cancer in men and it is responsible for about 10% of all cancer mortalities in both American and Canadian men. At present, serum prostate-specific antigen levels remain the most commonly used test to detect prostate cancer, and the standard and definitive diagnosis of the disease is via prostate biopsy. Conventional tissue biopsies are usually invasive, expensive, painful, time-consuming, and unsuitable for screening and need to be consistently evaluated by expert pathologists and have limited repeatability. Consequently, liquid biopsies are emerging as a favourable alternative to conventional tissue biopsies, providing a non-invasive and cost-effective approach for screening, diagnosis, treatment and monitoring of prostate cancer patients. Materials and methods: We searched several databases from August to December 2020 for relevant studies published in English between 2000 and 2020 and reporting on liquid-based biomarkers available in detectable quantities in patient bodily fluid samples. In this narrative review paper, we describe seven novel and promising liquid-based biomarkers that potentially account for individual patient variability as well as used in disease risk assessment, screening for early disease detection and diagnosis, identification of patients’ risk for metastatic disease and subsequent relapse, monitoring patient response to specific treatment and providing clinicians the potential to stratify patients likely to benefit from a particular treatment. Conclusions: The concept of precision medicine from prevention to treatment techniques that take individual patient variability into account will depend on the development of effective clinical biomarkers that interrogate key aberrant pathways potentially targetable with molecular targets or immunologic therapies. Liquid-based biomarkers with high sensitivity and specificity for prostate cancer are emerging as minimally invasive, lower risk, readily obtainable and easily repeatable technique for screening for early disease detection and diagnosis, patient stratification at diagnosis into different risk categories, identification of patients’ risk for metastatic disease and subsequent relapse, and real-time monitoring of patient response to specific treatment. Thus, effective liquid-based biomarkers will potentially shift the treatment paradigm of prostate cancer towards more personalised and targeted medicine.

Correction to: The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine?

An amendment to this paper has been published and can be accessed via the original article.

The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine?

The acute respiratory distress syndrome (ARDS) is a severe lung disorder with a high morbidity and mortality which affects all age groups. Despite active research with intense, ongoing attempts in developing pharmacological agents to treat ARDS, its mortality rate remains unaltered high and treatment is still only supportive. Over the years, there have been many attempts to identify meaningful subgroups likely to react differently to treatment among the heterogenous ARDS population, most of them unsuccessful. Only recently, analysis of large ARDS cohorts from randomized controlled trials have identified the presence of distinct biological subphenotypes among ARDS patients: a hypoinflammatory (or uninflamed; named P1) and a hyperinflammatory (or reactive; named P2) subphenotype have been proposed and corroborated with existing retrospective data. The hyperinflammatory subphenotyope was clearly associated with shock state, metabolic acidosis, and worse clinical outcomes. Core features of the respective subphenotypes were identified consistently in all assessed cohorts, independently of the studied population, the geographical location, the study design, or the analysis method. Additionally and clinically even more relevant treatment efficacies, as assessed retrospectively, appeared to be highly dependent on the respective subphenotype. This discovery launches a promising new approach to targeted medicine in ARDS. Even though it is now widely accepted that each ARDS subphenotype has distinct functional, biological, and mechanistic differences, there are crucial gaps in our knowledge, hindering the translation to bedside application. First of all, the underlying driving biological factors are still largely unknown, and secondly, there is currently no option for fast and easy identification of ARDS subphenotypes. This narrative review aims to summarize the evidence in biological subphenotyping in ARDS and tries to point out the current issues that will need addressing before translation of biological subohenotypes into clinical practice will be possible.

Neurodegenerative diseases and their related treatment

Aging is a phenomenon related to every person and has a tremendous impact on people’s life quality. During aging, some people may get neurodegenerative diseases, like Alzheimer’s disease. These diseases can vastly impair patient’s life quality and cause problems to their families. This review investigates and concludes many recent findings to find the symptoms, pathways, and possible cures for such diseases. The passage shows that changes happen at people’s gene, special protein function, and brain structure are closely related to such diseases. Consistent with such opinions, this review concludes what symptoms patients may have, such as Aβ’s accumulation and tau protein’s hyperphosphorylation, degeneration of basal ganglia. This review also focuses on the possible ways to cure the diseases or release their symptoms. At last, in light of the knowledge we have about neurodegenerative diseases, a more comprehensive understanding of the critical parts involved in these diseases can be obtained, indicating possibilities of producing more closely targeted medicine and treatment.