ABSTRACT
It raises questions about the impact of lard on the health and the differences in individual responses. Therefore, we developed a model of mice fed with high fat (HF) from lard in 130 days. The weight of the mice was measured every two days. Glucose tolerance test and insulin tolerance tests were performed at 70 days and 130 days of experiment. At the end of the study, the fat tissue was collected to check the weight, and a blood sample was collected to check the blood lipids and liver enzymes. Surprisingly, mice responded variously to the HF by being classified into two groups, one group had significantly high gained weight (HG_HF) versus the mice fed a standard diet (STD) (p < 0.001), and another group (LG_HF) has not difference in body weight compared to the STD groups. This phenomenon in body weight is directly reflected by the white fat accumulation, but not by brown fat. Eating HF from lard for a long time can disrupt glucose tolerance and cause dyslipidemia in mice, even in the LG_HF group, but can not disrupt insulin tolerance and cause liver enzyme disorders. In summary, our findings are a wake-up call for many cases where eating HF from lard does not gain weight and not increase the white fat storage, but still has the potential to cause adverse health effects. Further studies are encouraged to understand the molecular mechanisms that causes the body to regulate its weight and responses when eating HF from lard, especially in the LG_HF group.
ABSTRACT
OBJECTIVE: The obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aimed to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia. METHODS: Medline, CINAHL, PsycINFO, and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from the perspectives of both health care professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analyzed according to the methodology of Thomas and Harden. RESULTS: A total of 26 articles were included in this review. From patient perspectives, 3 main themes were identified: factors influencing poor eating behavior, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiologic limitations to exercise, and low health literacy. Rigid sociocultural norms and lack of accessible health care services, exercise facilities, and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support, and patient motivation impeded patients' weight loss attempts but were unaware of the other barriers they faced. CONCLUSION: There are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population level, primary care, and personal interventions are required to address this disparity, and enhanced health literacy can improve weight loss outcomes.
Subject(s)
Obesity , Overweight , Humans , Overweight/therapy , Obesity/therapy , Exercise , Weight Loss , Health PersonnelABSTRACT
Ear mesenchymal stem cells (EMSCs) have been investigated to differentiate into adipocytes, chondrocytes, and muscle cells in vitro. However, the factors controlling adipogenesis of this stem cell population in vitro, function, and type of adipocytes raised from them are still unclear. Here we found that genetics have a modest effect on adipogenic capacity of EMSCs. Adipocytes differentiated from EMSCs have a potential function in lipid metabolism as indicated by expression of lipogenic genes and this function of EMSC adipocytes is regulated by genetics. EMSCs failed to be differentiated into brite/brown adipocytes due to their lack of a thermogenic program, but adipocytes raised from EMSCs showed a fate of white adipocytes. Overall, our data suggest that EMSCs differentiate into functional white adipocytes in vitro and this is genetic-dependent.
Subject(s)
Adipocytes, Beige/metabolism , Adipocytes, Brown/metabolism , Adipogenesis/genetics , Antigens, Differentiation , Ear , Genetic Variation , Mesenchymal Stem Cells/metabolism , Animals , Antigens, Differentiation/genetics , Antigens, Differentiation/metabolism , Mice , Mice, TransgenicABSTRACT
Nigella sativa seed and its active compounds have been historically recognized as an effective herbal panacea that can establish a balanced inflammatory response by suppressing chronic inflammation and promoting healthy immune response. The essential oil and other preparations of N. sativa seed have substantial therapeutic outcomes against immune disturbance, autophagy dysfunction, oxidative stress, ischemia, inflammation, in several COVID-19 comorbidities such as diabetes, cardiovascular disorders, Kawasaki-like diseases, and many bacterial and viral infections. Compelling evidence in the therapeutic efficiency of N. sativa along with the recent computational findings is strongly suggestive of combating emerged COVID-19 pandemic. Also, being an available candidate in nutraceuticals, N. sativa seed oil could be immensely potential and feasible to prevent and cure COVID-19. This review was aimed at revisiting the pharmacological benefits of N. sativa seed and its active metabolites that may constitute a potential basis for developing a novel preventive and therapeutic strategy against COVID-19. Bioactive compounds of N. sativa seed, especially thymiquinone, α-hederin, and nigellidine, could be alternative and promising herbal drugs to combat COVID-19. Preclinical and clinical trials are required to delineate detailed mechanism of N. sativa's active components and to investigate their efficacy and potency under specific pathophysiological conditions of COVID-19.
Subject(s)
COVID-19 Drug Treatment , Nigella sativa/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , Benzoquinones , Diabetes Mellitus/drug therapy , Dietary Supplements , Humans , Oleanolic Acid/analogs & derivatives , Pandemics , SaponinsABSTRACT
BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.
Subject(s)
Drowning , Global Burden of Disease , Bangladesh/epidemiology , Child , China/epidemiology , Drowning/mortality , Female , Global Health , Humans , India/epidemiology , Male , Quality-Adjusted Life YearsABSTRACT
Bone marrow mesenchymal stem/stromal cells (BMSCs), which are known as multipotent cells, are widely used in the treatment of various diseases via their self-renewable, differentiation, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of BMSCs therapy in clinical applications. The number of clinical trials in phase I/II is accelerating; however, they are limited in the size of subjects, regulations, and standards for the preparation and transportation and administration of BMSCs, leading to inconsistency in the input and outcome of the therapy. Based on the International Society for Cellular Therapy guidelines, the characterization, isolation, cultivation, differentiation, and applications can be optimized and standardized, which are compliant with good manufacturing practice requirements to produce clinical-grade preparation of BMSCs. This review highlights and updates on the progress of production, as well as provides further challenges in the studies of BMSCs, for the approval of BMSCs widely in clinical application.
Subject(s)
Cell Culture Techniques/methods , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Animals , Bone Marrow , Bone Marrow Cells/cytology , Cell Culture Techniques/instrumentation , Cell Differentiation , Cell Proliferation , Cells, Cultured , Humans , Multipotent Stem Cells/cytologyABSTRACT
Vietnam, Laos, and Cambodia have reported first cases of Zika virus (ZIKV) infection since 2010 (Cambodia) and 2016 (Vietnam and Laos). One case of ZIKV-related microcephaly was recognized among a hundred infected cases in these areas, raising a great concern about the health risk related to this virus infection. At least 5 cases of ZIKV infection among travelers to Vietnam, Laos, and Cambodia were recorded. It is noticeable that ZIKV in these areas can cause birth defects. This work aims to discuss the current epidemics of ZIKV in Vietnam, Laos, and Cambodia and update the infection risk of ZIKV for travelers to these areas.
Subject(s)
Epidemics , Travel , Zika Virus Infection/epidemiology , Cambodia/epidemiology , Disease Outbreaks/statistics & numerical data , Humans , Laos/epidemiology , Microcephaly/virology , Risk Factors , Vietnam/epidemiology , Zika Virus Infection/complicationsABSTRACT
In recent decades, exceeding 60% of infectious cases in human beings are originated from pathogenic agents related to feral or companion animals. This figure continues to swiftly increase due to excessive exposure between human and contaminated hosts by means of applying unhygienic farming practices throughout society. In Asia countries-renowned for lax regulation towards animal-trading markets-have experienced tremendous outbreaks of zoonotic diseases every year. Meanwhile, various epidemic surges were first reported in the residential area of China-one of the largest distributor of all animal products on the planet. Some noticeable illnesses comprising of A/H5N1 or H7N9-known as avian influenza which transmitted from poultry and also wild birds-have caused inevitable disquiet among inhabitants. Indeed, poultry farming industry in China has witnessed dynamic evolution for the past two decades, both in quantity and degree of output per individual. Together with this pervasive expansion, zoonotic diseases from poultry have incessantly emerged as a latent threat to the surrounding residents in entire Asia and also European countries. Without strict exporting legislation, Vietnam is now facing the serious problem in terms of poultry distribution between the two countries' border. Even though several disease investigations have been conducted by many researchers, the disease epidemiology or transmission methods among people remained blurred and need to be further elucidated. In this paper, our aim is to provide a laconic review of common zoonotic diseases spread in Vietnam, outstanding cases and several factors predisposing to this alarming situation.
Subject(s)
Bird Diseases/epidemiology , Bird Diseases/transmission , Zoonoses/epidemiology , Zoonoses/transmission , Animals , Birds , Humans , Risk Factors , Vietnam/epidemiologyABSTRACT
Southeast Asia is considered one of worldwide hotspots consisting many distinct zoonotic infections. With optimal condition for the development of various pathogens, Vietnam is facing serious risks of zoonotic diseases. Besides, more than 50% Vietnamese people settle in rustic areas and earn their livings through small-scale animal breeding. It is possible that zoonotic diseases can be easily spread to the population by close contact with the infected animals, their infected residues, contaminated water, soil, or other possible means of transmission. In fact, zoonotic infections-transmissible infections between vertebrate animals and humans-cover a wide range of diseases with distinctive clinical and epidemiological highlights. With insufficient understanding and swift alteration in toxicity of the pathogens, these infections have gained more concerns due to sophisticated routes of transmission and harmful threats to humans. Recently emerging viral diseases exerted potential dangers to human beings, which required many countries to impose immediate actions to prevent any complications. Vietnam has recorded several cases of zoonotic diseases, especially pig-related illnesses; however, the studies on these diseases in this country remain limited. This work aims to highlight the zoonotic diseases transferring from pigs to humans and discuss risk factors of these diseases in Vietnam.
Subject(s)
Communicable Diseases, Emerging/transmission , Swine Diseases/transmission , Zoonoses/transmission , Animals , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Humans , Risk Factors , Swine , Swine Diseases/microbiology , Swine Diseases/parasitology , Swine Diseases/virology , Vietnam/epidemiology , Zoonoses/epidemiology , Zoonoses/prevention & controlABSTRACT
Developmental defects of enamel (DDE) are induced and regulated by several factors including genetics and the environment. There is evidence showing that dioxin in polluted areas has a strong effect on the health and development of teeth. However, there has been no study on DDE in the dioxin-affected regions in Vietnam. To identify the effect of dioxin on the prevalence of DDE in studied areas in Vietnam, a cross-sectional study was conducted in 2200 adults in the A Luoi district in the Thua Thien Hue province (the dioxin-affected region) and in the Kim Bang district in the Ha Nam province (dioxin-unaffected region) in 2015. All subjects were interviewed using a structured questionnaire and their teeth were examined and scored for enamel defects based on the 1992 FDI criteria. The defected teeth were then photographed. Our results showed that the DDE rate in A Luoi was 20.5% when measured as mouth prevalence and 5.8% when measured as tooth prevalence, while the rates in Kim Bang were 10.4 and 2.32% for mouth and tooth prevalence, respectively. Demarcated opacities were predominated in both districts (45.5% in A Luoi and 52.2% in Kim Bang). The DDE rate of the anterior teeth group was higher than that of the posterior teeth group. Most lesions presented on the buccal surface of the tooth. Overall, the DDE prevalence in the dioxin-affected region was 2.2 times higher than that in non-dioxin-affected region in the studied regions in Vietnam.
Subject(s)
Dental Enamel Hypoplasia/chemically induced , Dental Enamel Hypoplasia/epidemiology , Dioxins/toxicity , Environmental Exposure/adverse effects , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Surveys and Questionnaires , Vietnam/epidemiologyABSTRACT
The selective expression of CD137 on cells of the immune system (e.g., T and DC cells) and oncogenic cells in several types of cancer leads this molecule to be an attractive target to discover cancer immunotherapy. Therefore, specific antibodies against CD137 are being studied and developed aiming to activate and enhance anti-cancer immune responses as well as suppress oncogenic cells. Accumulating evidence suggests that anti-CD137 antibodies can be used separately to prevent tumor in some cases, while in other cases, these antibodies need to be co-administered with other antibodies or drugs/vaccines/regents for a better performance. Thus, in this work, we aim to update and discuss current knowledge about anti-cancer effects of anti-CD137 antibodies as mono- and combined-immunotherapies.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Molecular Targeted Therapy , Neoplasms/drug therapy , Tumor Necrosis Factor Receptor Superfamily, Member 9/antagonists & inhibitors , Animals , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Combined Modality Therapy , Humans , Immunotherapy , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/methods , Neoplasms/immunology , Neoplasms/metabolism , Treatment Outcome , Tumor Necrosis Factor Receptor Superfamily, Member 9/agonists , Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolismABSTRACT
BACKGROUND: MicroRNAs (miRNAs) have been shown to play an important role in pathological initiation, progression and maintenance. Because identification in the laboratory of disease-related miRNAs is not straightforward, numerous network-based methods have been developed to predict novel miRNAs in silico. Homogeneous networks (in which every node is a miRNA) based on the targets shared between miRNAs have been widely used to predict their role in disease phenotypes. Although such homogeneous networks can predict potential disease-associated miRNAs, they do not consider the roles of the target genes of the miRNAs. Here, we introduce a novel method based on a heterogeneous network that not only considers miRNAs but also the corresponding target genes in the network model. RESULTS: Instead of constructing homogeneous miRNA networks, we built heterogeneous miRNA networks consisting of both miRNAs and their target genes, using databases of known miRNA-target gene interactions. In addition, as recent studies demonstrated reciprocal regulatory relations between miRNAs and their target genes, we considered these heterogeneous miRNA networks to be undirected, assuming mutual miRNA-target interactions. Next, we introduced a novel method (RWRMTN) operating on these mutual heterogeneous miRNA networks to rank candidate disease-related miRNAs using a random walk with restart (RWR) based algorithm. Using both known disease-associated miRNAs and their target genes as seed nodes, the method can identify additional miRNAs involved in the disease phenotype. Experiments indicated that RWRMTN outperformed two existing state-of-the-art methods: RWRMDA, a network-based method that also uses a RWR on homogeneous (rather than heterogeneous) miRNA networks, and RLSMDA, a machine learning-based method. Interestingly, we could relate this performance gain to the emergence of "disease modules" in the heterogeneous miRNA networks used as input for the algorithm. Moreover, we could demonstrate that RWRMTN is stable, performing well when using both experimentally validated and predicted miRNA-target gene interaction data for network construction. Finally, using RWRMTN, we identified 76 novel miRNAs associated with 23 disease phenotypes which were present in a recent database of known disease-miRNA associations. CONCLUSIONS: Summarizing, using random walks on mutual miRNA-target networks improves the prediction of novel disease-associated miRNAs because of the existence of "disease modules" in these networks.
Subject(s)
Disease/genetics , Gene Regulatory Networks , MicroRNAs/metabolism , Algorithms , HumansABSTRACT
OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of mitochondria. It was recently also shown to locate on lipid droplets in adipocytes where it functions as an A-kinase anchoring protein (AKAP) that mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of perilipin (Plin1). In brown adipocytes indirect evidence support the notion that OPA1 regulation of fission serves to increase thermogenesis, which thereby contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid droplets serves as a gatekeeper to control lipolysis induced by adrenergic agonists. However, the function of OPA1 in lipolysis and thermogenesis in inducible brown adipocytes (brite/beige cells) remains elusive. Here we discuss the role of OPA1 in lipid metabolism.
Subject(s)
Adipocytes, Brown/metabolism , GTP Phosphohydrolases/metabolism , Lipolysis/physiology , Thermogenesis/physiology , Animals , Cyclic AMP-Dependent Protein Kinases/metabolism , Humans , Perilipin-1/metabolismABSTRACT
Obesity is an induced health problem that human beings have been facing with non-optimal treatment so far. Humans are on average getting fatter with age, and obesity and aging interact each other to shorten lifetime and decrease life quality. Obesity also causes several aging related-disorders such as cancer, strokes, cardiovascular disease, high blood pressure and type 2 diabetes. So, the molecular connections between aging and obesity are promising targets for bio-medical researches and innovative therapies of many health problems. In this review, we discuss the findings of adipose p53 and Rb-two central molecular linkages between aging and obesity-on lipid metabolism and obesity.
Subject(s)
Adipose Tissue/physiopathology , Aging , Obesity/physiopathology , Retinoblastoma Protein/physiology , Tumor Suppressor Protein p53/physiology , Animals , Homeostasis , Humans , MiceABSTRACT
Zika virus infection and its associated microcephaly have being receiving global concern. This infection has spread widely since the first outbreak was recorded in Africa in 1952. Now, it has been reported in over 70 countries on five continents including Africa, North and South America, Asia, and Europe. Vietnam is one of the most recent countries which had cases of Zika virus infection at the end of 2016. This country has also reported the first case of a microcephaly-born baby which was probably linked to Zika virus infection. However, information on the Zika virus epidemic in Vietnam is still limited. This brief report intends to update the current Zika virus epidemic, and to discuss challenges and perspectives in controlling this infection in Vietnam.
Subject(s)
Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Zika Virus/classification , Aedes/virology , Animals , Disease Outbreaks , Disease Vectors , Humans , Vietnam/epidemiology , Zika Virus/pathogenicity , Zika Virus Infection/drug therapy , Zika Virus Infection/virologyABSTRACT
In the study, osmotically dehydrated cherry tomatoes were partially dried to water activity between 0.746 and 0.868, vacuum-packed and stored at 4-30 °C for 60 days. Adaptive neuro-fuzzy inference system (ANFIS) was utilized to predict the physicochemical and microbiological parameters of these partially dried cherry tomatoes during storage. Satisfactory accuracies were obtained when ANFIS was used to predict the lycopene and total phenolic contents, color and microbial contamination. The coefficients of determination for all the ANFIS models were higher than 0.86 and showed better performance for prediction compared with models developed by response surface methodology. Through ANFIS modeling, the effects of storage conditions on the properties of partially dried cherry tomatoes were visualized. Generally, contents of lycopene and total phenolics decreased with the increase in water activity, temperature and storage time, while aerobic plate count and number of yeasts and molds increased at high water activities and temperatures. Overall, ANFIS approach can be used as an effective tool to study the quality decrease and microbial pollution of partially dried cherry tomatoes during storage, as well as identify the suitable preservation conditions.
ABSTRACT
A cohort of genes was selected to characterize the adipogenic phenotype in primary cell cultures from three tissue sources. We compared the quantitative expression of biomarkers in culture relative to their expression in vivo because the mere presence or absence of expression is minimally informative. Although all biomarkers analyzed have biochemical functions in adipocytes, the expression of some of the biomarkers varied enormously in culture relative to their expression in the adult fat tissues in vivo, i.e. inguinal fat for white adipocytes and brite cells, interscapular brown adipose tissue for brown adipocytes, and ear mesenchymal stem cells for white adipocytes from adult mice. We propose that the pattern of expression in vitro does not reflect gene expression in the adult mouse; rather it is predominantly the expression pattern of adipose tissue of the developing mouse between birth and weaning. The variation in gene expression among fat depots in both human and rodent has been an extensively studied phenomenon, and as recently reviewed, it is related to subphenotypes associated with immune function, the inflammatory response, fat depot blood flow, and insulin sensitivity. We suggest that adipose tissue biology in the period from birth to weaning is not just a staging platform for the emergence of adult white fat but that it has properties to serve the unique needs of energy metabolism in the newborn. A case in point is the differentiation of brite cells that occurs during this period followed by their involution immediately following weaning.
Subject(s)
Adipocytes/cytology , Adipocytes/metabolism , Adipose Tissue/growth & development , Biomarkers/metabolism , Gene Expression , Adipogenesis , Adipose Tissue/cytology , Adipose Tissue/metabolism , Animals , Cells, Cultured , Female , Humans , Mice , Mice, Inbred C57BL , Models, BiologicalABSTRACT
RNA therapeutics is a biological term regarding the usage of RNA-based molecules for medical purposes. Thanks to the success of mRNA-vaccine production against COVID-19, RNA therapeutics has gained more and more attention and investigation from worldwide scientists. It is considered as one of the promising alternatives for conventional drugs. In this first chapter, we presented an overview of the history and perspectives of RNA therapeutics' development. This chapter also explained the underlying mechanisms of different RNA-based molecules, including antisense oligonucleotide, interfering RNA (iRNA), aptamer, and mRNA, from degrading mRNA to inactivating targeted protein. Although there are many advantages of RNA therapeutics, its challenges in designing RNA chemical structure and the delivery vehicle need to be discussed. We described advanced technologies in the development of drug delivery systems that are positively correlated to the efficacy of the drug. Our aim is to provide a general background of RNA therapeutics to the audience before introducing plenty of more detailed parts, including clinical applications in certain diseases in the following chapters of the "RNA therapeutics" book.
Subject(s)
Drug Delivery Systems , Oligonucleotides, Antisense , Humans , RNA, Small Interfering , RNA, Messenger/genetics , RNA, Messenger/therapeutic useABSTRACT
Ovarian cancer is one of the diseases that have the highest mortality rate for women, especially women over 50 years old. In the future, incidence and mortality rates are predicted to extend in countries with low HDI. Instability in the structure and function of genetic factors has long been known as a cause of cancer, including ovarian cancer. Besides understanding gene mutations, epigenetic alterations have emerged as another aspect leading to the pathogenesis of ovarian neoplasm. The development and progression of this fatal disease have been found to be associated with abnormalities of epigenetic regulation. DNA methylation, histone modification, and non-coding RNAs-based gene silencing are processes of interest in developing ovarian carcinoma and are also new targets for cancer detection or treatment.
Subject(s)
Epigenesis, Genetic , Ovarian Neoplasms , Humans , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Female , DNA Methylation/genetics , Animals , Gene Expression Regulation, NeoplasticABSTRACT
The prevalence of metabolic disorders is increasing exponentially and has recently reached epidemic levels. Over the decades, a large number of therapeutic options have been proposed to manage these diseases but still show several limitations. In this circumstance, RNA therapeutics have rapidly emerged as a new hope for patients with metabolic diseases. 57 years have elapsed from the discovery of mRNA, a large number of RNA-based drug candidates have been evaluated for their therapeutic effectiveness and clinical safety under clinical studies. To date, there are seven RNA drugs for treating metabolic disorders receiving official approval and entering the global market. Their targets include hereditary transthyretin-mediated amyloidosis (hATTR), familial chylomicronemia syndrome, acute hepatic porphyria, primary hyperoxaluria type 1 and hypercholesterolemia, which are all related to liver proteins. All of these seven RNA drugs are antisense oligonucleotides (ASO) and small interfering RNA (siRNA). These two types of treatment are both based on oligonucleotides complementary to target RNA through Watson-Crick base-pairing, but their mechanisms of action include different nucleases. Such treatments show greatest potential among all types of RNA therapeutics due to consecutive achievements in chemical modifications. Another method, mRNA therapeutics also promise a brighter future for patients with a handful of drug candidates currently under development.