The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

RNA therapeutics for diarrhea.

Diarrhea is caused by a variety of bacterial and viral agents, inflammatory conditions, medications, and hereditary conditions. Secretory diarrhea involves several ion and solute transporters, activation of the cyclic nucleotide and Ca2+ signaling pathways, as well as intestinal epithelial secretion. In many cases of secretory diarrhea, activation of Cl- channels, such as the cystic transmembrane conduction regulator and the Ca2+stimulated Cl- channel fibrosis, promote secretion while concurrently inhibiting Na+ transport expressing fluid absorption. Current diarrhea therapies include rehydration and electrolyte replacement via oral rehydration solutions, as well as medications that target peristalsis or fluid secretion. The rising understanding of RNA function and its importance in illness has encouraged the use of various RNAs to operate selectively on "untreatable" proteins, transcripts, and genes. Some RNA-based medications have received clinical approval, while others are currently in research or preclinical studies. Despite major obstacles in the development of RNA-based therapies, many approaches have been investigated to improve intracellular RNA trafficking and metabolic stability.

RNA therapeutics for metabolic disorders.

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.

RNA therapeutics for respiratory diseases.

It has become increasingly common to utilize RNA treatment to treat respiratory illnesses. Experimental research on both people and animals has advanced quickly since the turn of the twenty-first century in an effort to discover a treatment for respiratory ailments that could not be accomplished with earlier techniques, specifically in treating prevalent respiratory diseases such as lung cancer, chronic obstructive pulmonary disease (COPD), respiratory infections caused by viruses, and asthma. This chapter has provided a comprehensive overview of the scientific evidence in applying RNA therapy to treat respiratory diseases. The chapter describes the development of this therapy for respiratory diseases. At the same time, the types of RNA therapy for respiratory diseases have been highlighted. In addition, the mechanism of this therapy for respiratory diseases has also been covered. These insights are indispensable if this therapy is to be developed widely.

RNA therapeutics for disorders of excretory system.

The excretory system is responsible for removing wastes from the human body, which plays a crucial role in our lives. Current treatments for diseases related to this system have shown several limitations; therefore, there is a rising need for novel methods. In this circumstance, RNA-based therapeutics have rapidly emerged as new and promising candidates. In fact, to date, a handful of potential drugs have passed the development step and entered the clinical pipeline. Among them, one drug received FDA approval to enter the global market, which is Oxlumo (Lumasiran) for the treatment of primary hyperoxaluria type 1. For other excretory diseases, such as paroxysmal nocturnal hemoglobinuria, urothelial cancer or renal cancer, RNA-based candidates are also being tested under clinical trials. Currently, the most potential types of RNA therapeutics to treat disorders of the excretory system are those based on small interfering RNA (siRNA), antisense oligonucleotides (ASO) and messenger RNA (mRNA), Among them, siRNA therapeutics seem to be the most promising, including Oxlumo and two other developing drug candidates. This chapter will provide a general overview on the application of RNA therapeutics in disorders of the excretory system.

Phage for cancer therapy.

Cancer is currently a global health challenge, characterized by dysfunction of organs due to the uncontrolled growth of cells exponentially. The therapies used to treat cancer in patients so far are widely used. However, there are also some problems, such as the high cost of surgery and chemotherapy. Thus, there are many barriers to care for patients with cancer, especially in low and middle-income countries. In addition, the many risks and adverse effects of radiation treatment. Therefore, to reduce mortality in patients with the disease, we need a newer therapy with more targeted treatment, fewer side effects, and cheaper cost. The application of bacteria in cancer treatment was first developed in 1983. Currently, this therapy is attracting the attention of scientists due to its great potential in cancer treatment. This chapter discusses the successful research on the bacteriophage for cancer, the mechanism and its potential. In addition, some types of bacteria that are most important for cancer treatment and limitations on the widespread application of this therapy were also mentioned. Reviewing all the researches on bacteriotherapy in cancer are essential to increase the knowledge in this area and make this therapy more optimal in the future.

Epigenetics in cancer development, diagnosis and therapy.

Cancer is a dangerous disease and one of the leading causes of death in the world. In 2020, there were nearly 10 million cancer deaths and approximately 20 million new cases. New cases and deaths from cancer are expected to increase further in the coming years. To have a deeper insight into the mechanism of carcinogenesis, epigenetics studies have been published and received much attention from scientists, doctors, and patients. Among alterations in epigenetics, DNA methylation and histone modification are studied by many scientists. They have been reported to be a major contributor in tumor formation and are involved in metastasis. From the understanding of DNA methylation and histone modification, effective, accurate and cost-effective methods for diagnosis and screening of cancer patients have been introduced. Furthermore, therapeutic approaches and drugs targeting altered epigenetics have also been clinically studied and have shown positive results in combating tumor progression. Several cancer drugs that rely on DNA methylation inactivation or histone modification have been approved by the FDA for the treatment of cancer patients. In summary, epigenetics changes such as DNA methylation or histone modification are take part in tumor growth, and they also have great prospect to study diagnostic and therapeutic methods of this dangerous disease.

Frizzled receptors and SFRP5 in lipid metabolism: Current findings and potential applications.

Lipid metabolism plays a very important role as the central metabolic process of the body. Lipid metabolism interruptions may cause many chronic diseases, for example, non-alcoholic fatty liver disease (NAFLD), diabetes, and obesity. Secreted Frizzled Related Protein 5 (SFRP5) and Frizzled receptors (FZD) are two newly discovered adipokines that are involved in lipid metabolism as well as lipogenesis. Both of these adipokines affect lipid metabolism and adipogenesis through three WNT signaling pathways (WNTSP): WNT/ß-catenin, WNT/Ca2+, and WNT/JNK. FZD consists of 10 species, which have a cysteine-rich domain (CRD) to bind to the WNT protein for signal transduction. Depending on the type of ligand or co-receptor, they can stimulate or inhibit adipogenesis. In lipid metabolism, they play a role in recognizing fatty acids. In obesity, gene expression of the WNT/FZD receptors is significantly increased. In contrast, SFPR5 serves as an antagonist that can compete with FZD for inhibition of WNTSP. It is believed to have anti-inflammatory potential in obesity and diseases related to abnormal lipid metabolism. In these cases, the expression of SFRP5 is found to be very low leading to the promoted production of proinflammatory cytokines (PICS). Some methods that include using recombinant SFRP5 to improve non-alcoholic steatohepatitis (NASH), using secreted Ly-6/uPAR-related protein 1 (Slurp1) to regulate fat accumulation in the liver through SFRP5, and dietary and lifestyle interventions to improve overweight/obesity have been studied. However, understandings of the molecular mechanisms of these two adipokines and their interactions are very limited. Therefore, more in-depth studies are needed in the future.

The expression and mutation of BRCA1/2 genes in ovarian cancer: a global systematic study.

INTRODUCTION: This systematic review was designed to summarize the findings on expression and mutation of BRCA1/2 genes in ovarian cancer (OC) patients, focusing on mutation detection technology and taking clinical decisions for better treatment. AREAS COVERED: We conducted a systematic review by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses document selection guidelines for the document selection process and the PICOT standard for developing the keywords to search for. A total of 5729 publications were included, and 50 articles were put into the final screening. The results showed that Next-Generation Sequencing was a breakthrough technology in detecting Breast Cancer 1/2 (BRCA1/2) gene mutations because of its efficacy and affordability. Other technologies are also being applied now for mutation detection. The most prominent associations of BRCA1/2 gene mutations were age, heredity, and family history. Furthermore, mutations of BRCA1/2 could improve survival rate and overall survival. There is no sufficient study available to conclude a systematic analysis for the expression of BRCA1/2 gene in OC. EXPERT OPINION: Research will continue to develop more diagnostic techniques based on the expression and mutation of BCRA1/2 genes for OC in the near future.

Exploring the Potential of Stem Cell-Based Therapy for Aesthetic and Plastic Surgery.

Over the last decade, stem cell-associated therapies are widely used because of their potential in self-renewable and multipotent differentiation ability. Stem cells have become more attractive for aesthetic uses and plastic surgery, including scar reduction, breast augmentation, facial contouring, hand rejuvenation, and anti-aging. The current preclinical and clinical studies of stem cells on aesthetic uses also showed promising outcomes. Adipose-derived stem cells are commonly used for fat grafting that demonstrated scar improvement, anti-aging, skin rejuvenation properties, etc. While stem cell-based products have yet to receive approval from the FDA for aesthetic medicine and plastic surgery. Moving forward, the review on the efficacy and potential of stem cell-based therapy for aesthetic and plastic surgery is limited. In the present review, we discuss the current status and recent advances of using stem cells for aesthetic and plastic surgery. The potential of cell-free therapy and tissue engineering in this field is also highlighted. The clinical applications, advantages, and limitations are also discussed. This review also provides further works that need to be investigated to widely apply stem cells in the clinic, especially in aesthetic and plastic contexts.

Gut microbiota in gastrointestinal diseases.

Gut microbiota is a highly dense population of different kinds of bacteria residing in the gut which co-evolves with the host. It engages in a number of metabolic and immunological activities. Gut microbiota is associated with maintenance of health, and unbalanced microbiota contributes in the development of several diseases. Alteration of beneficial gut microbiota population triggers gastrointestinal diseases including irritable bowel syndrome, inflammatory bowel disease, celiac disease, colorectal cancer, and many others. Gut microbiota can be affected by multiple factors such as diet, stress, genetic variations. In this chapter, we highlight how gut microbiota plays a key role in pathogenesis of gastrointestinal disease.

Current approaches in CRISPR-Cas9 mediated gene editing for biomedical and therapeutic applications.

A single gene mutation can cause a number of human diseases that affect the quality of life. Until the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) systems, it was challenging to correct a gene mutation to avoid a disease by reverting phenotypes. The advent of CRISPR technology has changed the field of gene editing, given its simplicity and intrinsic programmability, surpassing the limitations of both zinc-finger nuclease and transcription activator-like effector nuclease and becoming the method of choice for therapeutic gene editing by overcoming the bottlenecks of conventional gene-editing techniques. Currently, there is no commercially available medicinal cure to correct a gene mutation that corrects and reverses the abnormality of a gene's function. Devising reprogramming strategies for faithful recapitulation of normal phenotypes is a crucial aspect for directing the reprogrammed cells toward clinical trials. The CRISPR-Cas9 system has been promising as a tool for correcting gene mutations in maladies including blood disorders and muscular degeneration as well as neurological, cardiovascular, renal, genetic, stem cell, and optical diseases. In this review, we highlight recent developments and utilization of the CRISPR-Cas9 system in correcting or generating gene mutations to create model organisms to develop deeper insights into diseases, rescue normal gene functionality, and curb the progression of a disease. Delivery of CRISPR-components being a pivotal aspect in proving its effectiveness, various proven delivery systems have also been briefly discussed.

Advances in microfluidics devices and its applications in personalized medicines.

Microfluidics is an exponentially growing area and is being used for numerous applications from basic science to advanced biotechnology and medicines. Microfluidics provides a platform to the research community for studying and building new strategies for the diagnosis and therapeutics applications. In the last decade, microfluidic have enriched the field of diagnostics by providing new solutions which was not possible with conventional detection and treatment methods. Microfluidics has the ability to precisely control and perform high-throughput functions. It has been proven as an efficient and rapid method for biological sample preparation, analysis and controlled drug delivery system. Microfluidics plays significant role in personalized medicine. These personalized medicines are used for medical decisions, practices and other interventions as well as for individual patients based on their predicted response or risk of disease. This chapter highlights microfluidics in developing personalized medical applications for its applications in diseases such as cancer, cardiovascular disease, diabetes, pulmonary disease and several others.

Adipogenesis of ear mesenchymal stem cells (EMSCs): adipose biomarker-based assessment of genetic variation, adipocyte function, and brown/brite differentiation.

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.

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Evaluation of Hepatic Fibrosis and Steatosis Using Fibroscan.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major guidelines. Transient elastography using FibroScan with CAP (controlled attenuation parameter) can assess both liver steatosis and fibrosis simultaneously. This paper took a new look at the prevalence of NAFLD and the severity of fibrosis among T2DM patients in Vietnam. The study was conducted using a cross-sectional design in T2DM adults who attended Dai Phuoc Ho Chi Minh Polyclinic and Polyclinic of Pham Ngoc Thach University of Medicine. Liver steatosis and fibrosis was assessed by FibroScan. NAFLD was diagnosed if CAP > 233 dB/m (steatosis > 5%). Data were analyzed using STATA 12 software program. We found that a total of 307 type 2 diabetic patients qualified for the study's criteria. The prevalence of NAFLD in T2DM patients based on FibroScan was 73.3%. Rates of mild, moderate and severe steatosis were 20.5%, 21.8% and 30.9%, respectively. The prevalence of significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) was 13.0%, 5.9% and 3.6%, respectively. On multivariate analysis, aspartate aminotransferase (AST) (OR: 1.067; 95% CI: 1.017-1.119; p = 0.008) and platelet levels (OR: 0.985; 95% CI: 0.972-0.999; p = 0.034) were independent of risk factors of advanced fibrosis. Thus, our study supports screening for NAFLD and for evaluating the severity of liver fibrosis in T2DM patients.

Advanced in developmental organic and inorganic nanomaterial: a review.

With the unique properties such as high surface area to volume ratio, stability, inertness, ease of functionalization, as well as novel optical, electrical, and magnetic behaviors, nanomaterials have a wide range of applications in various fields with the common types including nanotubes, dendrimers, quantum dots, and fullerenes. With the aim of providing useful insights to help future development of efficient and commercially viable technology for large-scale production, this review focused on the science and applications of inorganic and organic nanomaterials, emphasizing on their synthesis, processing, characterization, and applications on different fields. The applications of nanomaterials on imaging, cell and gene delivery, biosensor, cancer treatment, therapy, and others were discussed in depth. Last but not least, the future prospects and challenges in nanoscience and nanotechnology were also explored.

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.

Flow diverter stent for treatment of cerebral aneurysms: A report of 130 patients with 134 aneurysms.

BACKGROUND: This study aims to report our experience with cerebral aneurysms, which may improve in the treatment with the flow-diverter stent and follow up. METHODS: This study was conducted in a consecutive series of 130 patients. 134 procedures were performed for treating these patients in Hanoi Medical University Hospital and Bach Mai Hospital from January 2012 to April 2017. 143 flow diverter stents (Pipeline, FRED and SILK) were used. Aneurysm morphology, stent patency and cerebral parenchyma before and after intervention were analyzed on images of digital subtraction angiography (DSA), computed tomography (CT) and magnetic resonance (MR). The follow-up data after 3-6 months and 12 months were recorded. RESULTS: In 130 patients (31 men, 99 women), aneurysms of internal carotid artery were mostly common (92.6%), especially in cavernous (35.1%) and in para-ophthalmic (40.3%) segments. 83 cases (61.9%) had wide-neck aneurysms, and 16 cases (11.9%) had multiple aneurysms, and only 5 cases (3.7%) had blister-liked aneurysms. Endovascular treatment was successfully performed at rate of 94.8%. In 3 patients, the stent could not be delivered. Mortality and morbidity rates were 1.5% and 3.7%, respectively. MRI and MSCT follow-up at 3 months showed complete or incomplete occlusions of aneurysms was 7.4% or 17.5%, respectively. 3 patients experienced a thromboembolic event (4.3%). CONCLUSIONS: Intracranial aneurysms of cavernous and para-ophthalmic segments of internal carotid artery are mostly common with wide-neck and multi aneurysms. Deployment of flow diverter stent is safe and effective with high rate of successful and low procedural complications.

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells.

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.

Step-by-Step Protocol for Superparamagnetic Nanoparticle-Based Plasma Membrane Isolation from Eukaryotic Cell.

Here, we elaborate our detailed protocol for synthesis, functionalization, and application of superparamagnetic nanoparticle (SPMNP) for plasma membrane and lysosome isolation. We used standard thermal decomposition-based synthesis of iron oxide (Fe3O4) core SPMNP 1.0. Using ligand addition methodology, we surface functionalized SPMNP 1.0 with phospholipids and generated phospholipid-SPMNP 2.0. Further we used NH2-phospholipid-SPMNP 2.0 to isolate plasma membrane. Using our SPMNP subcellular fractionation protocol, we are able to isolate high-pure-high-yield plasma membrane using NH2-phospholipid-SPMNP 2.0. As a future perspective, we propose to use SPMNP on clinical patient samples and perform mass spectrometry-based proteomics, lipidomics, and glycomics for early cancer diagnosis.