Drug repurposing for regenerative medicine and cosmetics: Scientific, technological and economic issues.

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.

A eutectogels-catalyzed one-pot multi-component reaction: access to pyridine and chromene derivatives.

The demand for a wide array of functional chemicals and materials has experienced a significant surge in tandem with the advancement of civilization. Regrettably, a number of perilous solvents are employed in chemical laboratories and industrial settings, posing significant risks to the well-being of researchers and contributing to environmental degradation through pollution. Eutectogels, which are based on the eutectic concept, may be synthesized by self-assembling or self-polymerization of various components when put under UV irradiation (254 nm). A novel copolymeric deep eutectic solvent (DES) was successfully synthesized, comprising choline chloride (HBA) as the hydrogen bond acceptor, acetamide (HBD) as the hydrogen bond donor, tetraethyl orthosilicate (TEOS), and formic acid. In this study, we present the preparation of four-component ETGs for synthesizing pyridine and chromene derivatives as a reusable catalyst through a multi-component pathway without solvents. The procedure of synthesizing these heterocyclic compounds is free of using toxic solvents and it could be categorized as a green method.

Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting. Additionally, while the ELN 2022 guidelines appear to improve the prognostication of AML, clarification is needed to determine how the revision applies to lower-intensity strategies. To investigate this, we retrospectively analyzed the performance of venetoclax with decitabine or azacitidine in relapsed or refractory AML under the ELN 2022 guidelines. We demonstrated that the ELN 2022 revision is not optimized for lower-intensity venetoclax-based strategies. To refine the prognostication schema, we showed significantly improved response and survival benefits for patients with mutated NPM1 and IDH. Relatively, patients with mutated NRAS, KRAS, and FLT3-ITD were associated with inferior response and survival. Furthermore, there is an unmet clinical need for tools to improve the selection of lower-intensity therapy candidates with borderline functional status. Using an incremental survival computation method, we discovered that a CCI score threshold of 5 distinguishes patients at an elevated risk of death. Together, these novel findings highlight areas of refinement to improve survival in relapsed or refractory AML.

Enhancement of Visible Light Antibacterial Activities of Cellulose Fibers from Lotus Petiole Decorated ZnO Nanoparticles.

Cellulose/ZnO (CZ) nanocomposites are promising antimicrobial materials known for their antibiotic-free nature, biocompatibility, and environmental friendliness. In this study, cellulose fibers extracted from lotus petioles were utilized as a substrate and decorated with various shapes of ZnO nanoparticles (NPs), including small bean, hexagonal ingot-like, long cylindrical, and hexagonal cylinder-shaped NPs. Increasing zinc salt molar concentration resulted in highly crystalline ZnO NPs forming and enhanced interactions between ZnO NPs and -OH groups of cellulose. The thermal stability and UV-visible absorption properties of the CZ samples were influenced by ZnO concentration. Notably, at a ZnO molar ratio of 0.1, the CZ 0.1 sample demonstrated the lowest weight loss, while the optical band gap gradually decreased from 3.0 to 2.45 eV from the CZ 0.01 to CZ 1.0 samples. The CZ nanocomposites exhibited remarkable antibacterial activity against both Staphylococcus aureus (S. aureus, Gram-positive) and Escherichia coli (E. coli, Gram-negative) bacteria under visible light conditions, with a minimum inhibitory concentration (MIC) of 0.005 mg/mL for both bacterial strains. The bactericidal effects increased with higher concentrations of ZnO NPs, even achieving 100% inhibition. Incorporating ZnO NPs onto cellulose fibers derived from lotus plants presents a promising avenue for developing environmentally friendly materials with broad applications in antibacterial and environmental fields.

RNA therapeutics for treatment of diabetes.

Diabetes is an ongoing global problem as it affects health of more than 537 million people around the world. Diabetes leaves many serious complications that affect patients and can cause death if not detected and treated promptly. Some of the complications of diabetes include impaired vascular system, increased risk of stroke, neurological diseases that cause pain and numbness, diseases related to the retina leading to blindness, and other complications affecting kidneys, heart failure, muscle weakness, muscle atrophy. All complications of diabetes seriously affect the health of patients. Recently, gene therapy has emerged as a viable treatment strategy for various diseases. DNA and RNA are among the target molecules that can change the structure and function of proteins and are effective methods of treating diseases, especially genetically inherited diseases. RNA therapeutics has attracted deep interest as it has been approved for application in the treatment of functional system disorders such as spinal muscular atrophy, and muscular dystrophy. In this review, we cover the types of RNA therapies considered for treatment of diabetes. In particular, we delve into the mechanism of action of RNA therapies for diabetes, and studies involving testing of these RNA therapies. Finally, we have highlighted the limitations of the current understanding in the mechanism of action of RNA therapies.

Characterizing Neisseria meningitidis in Southern Vietnam between 2012 and 2021: A predominance of the chloramphenicol-resistant ST-1576 lineage.

Objectives: Our goal was to describe Invasive Meningococcal Disease (IMD) in Southern Vietnam over the last 10 years. We characterized 109 Neisseria meningitidis strains in Southern Vietnam isolated between 1980s to 2021, that were collected from IMD (n = 44), sexually transmitted infections (n = 2), and healthy carriage (n = 63). Methods: IMD were confirmed by bacterial culture and/or real-time polymerase chain reaction at the national reference laboratory in Pasteur Institute of Ho Chi Minh City (PIHCM). Antimicrobial resistance was determined on 31 IMD and two sexually transmitted infection isolates with E-test for chloramphenicol (CHL), penicillin (PEN), ciprofloxacin (CIP), ceftriaxone (CRO), and rifampicin (RIF). Sequencing was performed for analyzing of multilocus-sequence-typing (MLST), porA, fetA, and antibiotic resistance genes, including gyrA, penA, and rpoB. Results: The incidence rate during this period was 0.02 per 100,000 persons/year. Serogroup B accounted for over 90% of cases (50/54). ST-1576 were mainly responsible for IMD, 27/42 MLST profiles, and associated with CHL resistance. Resistance was prevalent among IMD isolates. Thirteen were resistant to CHL (minimum inhibitory concentration [MIC] ≥16 mg/l), 12 were intermediate to PEN (MIC between 0.19 and 0.5 mg/l), and five were CIP-resistant (MIC between 0.19 and 0.5 mg/l). Particularly, one was non-susceptible to CRO (MIC at 0.125 mg/l), belonging to ST-5571 lineage. The resistance was due to carrying resistant alleles of penA and gyrA genes, and catP gene. Notably, seven isolates were resistant/non-susceptible to two or more antibiotics. Conclusion: Our results suggest the persistence of the circulating ST-1576 in Southern Vietnam, with a spread of antimicrobial resistance across the community.

Dopant-Induced Charge Redistribution on the 3D Sponge-like Hierarchical Structure of Quaternary Metal Phosphides Nanosheet Arrays Derived from Metal-Organic Frameworks for Natural Seawater Splitting.

Dopant-induced electron redistribution on transition metal-based materials has long been considered an emerging new electrocatalyst that is expected to replace noble-metal-based electrocatalysts in natural seawater electrolysis; however, their practical applications remain extremely daunting due to their sluggish kinetics in natural seawater. In this work, we developed a facile strategy to synthesize the 3D sponge-like hierarchical structure of Ru-doped NiCoFeP nanosheet arrays derived from metal-organic frameworks with remarkable hydrogen evolution reaction (HER) performance in natural seawater. Based on experimental results and density functional theory calculations, Ru-doping-induced charge redistribution on the surface of metal active sites has been found, which can significantly enhance the HER activity. As a result, the 3D sponge-like hierarchical structure of Ru-NiCoFeP nanosheet arrays achieves low overpotentials of 52, 149, and 216 mV at 10, 100, and 500 mA cm-2 in freshwater alkaline, respectively. Notably, the electrocatalytic activity of the Ru-NiCoFeP electrocatalyst in simulated alkaline seawater and natural alkaline seawater is nearly the same as that in freshwater alkaline. This electrocatalyst exhibits superior catalytic properties with outstanding stability under a high current density of 85 mA cm-2 for more than 100 h in natural seawater, which outperforms state-of-the-art 20% Pt/C at high current density. Our work provides valuable guidelines for developing a low-cost and high-efficiency electrocatalyst for natural seawater splitting.

Childhood Bacterial Meningitis Surveillance in Southern Vietnam: Trends and Vaccination Implications From 2012 to 2021.

Background: This retrospective hospital-based surveillance aimed to assess the epidemiology, causative pathogens trend, and serotypes distribution of pneumococcal meningitis among children aged under 5 years with bacterial meningitis in Southern Vietnam after the introduction of pentavalent vaccine in the Expanded Program on Immunization (EPI). Methods: From 2012 to 2021, cerebrospinal fluid samples were collected from children aged under 5 years with suspected bacterial meningitis at Children's Hospitals 1 and 2 in Ho Chi Minh City. Probable bacterial meningitis (PBM) cases were identified using biochemistry and cytology. Real-time polymerase chain reaction was used to confirm cases of confirmed bacterial meningitis (CBM) caused by Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitidis. Streptococcus pneumoniae serotyping was performed. Results: Of the 2560 PBM cases, 158 (6.2%) were laboratory-confirmed. The CBM proportion decreased during the 10-year study and was associated with age, seasonality, and permanent residence. Streptococcus pneumoniae was the most common pathogen causing bacterial meningitis (86.1%), followed by H influenzae (7.6%) and N meningitidis (6.3%). The case-fatality rate was 8.2% (95% confidence interval, 4.2%-12.2%). Pneumococcal serotypes 6A/B, 19F, 14, and 23F were the most prevalent, and the proportion of pneumococcal meningitis cases caused by the 10-valent pneumococcal conjugate vaccine (PCV) serotypes decreased from 96.2% to 57.1% during the PCV eras. Conclusions: Streptococcus pneumoniae is the most frequent causative agent of bacterial meningitis in children aged under 5 years in Southern Vietnam over the last decade. Policymakers may need to consider introducing PCVs into the EPI to effectively prevent and control bacterial meningitis.

Promoting High-Oxidation-State Metal Active Sites in a Hollow Ternary Metal Fluoride Nanoflake Array for Urea Electrolysis.

The adsorption ability of hydrogen, hydroxide, and oxygenic intermediates plays a crucial role in electrochemical water splitting. Electron-deficient metal-active sites can prompt electrocatalytic activity by improving the adsorption ability of intermediates. However, it remains a significant challenge to synthesize highly abundant and stable electron-deficient metal-active site electrocatalysts. Herein, we present a general approach to synthesizing a hollow ternary metal fluoride (FeCoNiF2) nanoflake array as an efficient and robust bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). We find that the F anion withdraws electrons from the metal centers, inducing an electron-deficient metal center catalyst. The rationally designed hollow nanoflake array exhibits the overpotential of 30 mV for HER and 130 mV for UOR at a current density of 10 mA cm-2 and superior stability without decay events over 150 h at a large current density of up to 100 mA cm-2. Remarkably, the assembled urea electrolyzer using a bifunctional hollow FeCoNiF2 nanoflake array catalyst requires cell voltages of only 1.352 and 1.703 V to afford current densities of 10 and 100 mA cm-2, respectively, which are 116 mV less compared with that required for overall water splitting.

Advances in Hodgkin's lymphoma pharmacotherapy: a focus on histone deacetylase inhibitors.

INTRODUCTION: Classical Hodgkin lymphomas (cHL) usually have excellent cure rates. Yet, for patients with refractory or relapsed cHL, prognosis deteriorates as the disease becomes resistant to subsequent lines of therapies: autologous stem cell transplantation, brentuximab vedotin, and checkpoint inhibitors. Immune escape and drug resistance are hallmarks of Hodgkin Reed Sternberg cell survival, prompting the need for additional therapeutic strategies. Histone modification-based combination is an effective clinical strategy. AREAS COVERED: In this review, we discuss the different histone deacetylase (HDAC) inhibitor molecules that have been developed and studied in cancer therapy with a focus on cHL. We review their preclinical and clinical activities both as single agents and in combination studies. Literature search was conducted in PubMed, Google Scholar, and ClinicalTrials.gov databases, using search terms 'Hodgkin lymphoma,' 'histone deacetylase inhibitor', and variations on such (e.g. 'HDAC' and individual drug names) in combination using operators 'AND,' 'OR,' and 'NOT' according to Boolean logic. EXPERT OPINION: HDAC inhibitors alone will not be sufficient for the treatment of R/RcHL, but given their disease control capacity, synergistic interaction with currently approved drugs, and ability to overcome drug resistance, particularly PD-1 inhibitors, we believe that HDACinhibitors will eventually become incorporated into the treatment armamentarium of cHL.

Conversion of cellulose into valuable chemicals using sulfonated amorphous carbon in 1-ethyl-3-methylimidazolium chloride.

In this study, three carbon-based solid acid catalysts were prepared via the one-step hydrothermal procedure using glucose and Brønsted acid, including sulfuric acid, p-toluenesulfonic acid, or hydrochloric acid. The as-synthesized catalysts were tested for their ability to convert cellulose into valuable chemicals. The effects of Brønsted acidic catalyst, catalyst loading, solvent, temperature, time, and reactor on the reaction were investigated. The as-synthesized C-H2SO4 catalyst containing Brønsted acid sites (-SO3H, -OH, and -COOH functional groups) demonstrated high activity in the transformation of cellulose into valuable chemicals with the yield of total products of 88.17% including 49.79% LA in 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) solvent at 120 °C in 24 h. The recyclability and stability of C-H2SO4 were also observed. A proposed mechanism of cellulose conversion into valuable chemicals in the presence of C-H2SO4 was presented. The current method could provide a feasible approach for the conversion of cellulose into valuable chemicals.

Effects of career development learning on students' perceived employability: a longitudinal study.

This study investigates the relationship between career development learning (CDL) and students' perceived employability (SPE) with the mediating role of human capital. Using a quantitative method based on structured questionnaires to collect data from 512 Vietnamese students before starting their internship at businesses and 322 of them after 4 months, the results of the partial least square Structural Equational Model analysis showed that CDL positively affects SPE over time. Besides, the study explored the mediating effect of human capital in the relationship between CDL and SPE. In particular, scholastic capital and cultural capital play mediating roles while social capital failed to be in the relationship between CDL and SPE. This study is expected to enrich current literature on students' employability and human capital theory. From practical aspects, the findings of this work can be of benefit to higher education institutions in supporting their students to enhance their employability in labour market.

Posterior reversible encephalopathy syndrome in carcinoid tumor.

This case presents a patient with ectopic secretion of adrenocorticotrophic hormone from a carcinoid tumor resulting in severe hypertension, posterior reversible encephalopathy syndrome (PRES), and refractory status epilepticus. Secondary hypertension may be difficult to identify in critically ill patients. Severely uncontrolled hypertension presenting with PRES caused by Cushing syndrome is rare but should be considered. Management requires the correct diagnosis and specific treatment. A missed or delayed diagnosis can lead to serious consequences and disability.

COVID-19 in Southeast Asia: current status and perspectives.

Coronavirus Disease-2019 (COVID-19) has spread globally with catastrophic damages to the public health, social and economy since the beginning of the outbreak. In 2020, Southeast Asia proved that it could prevent the worst effects of a pandemic through the closure of activities and borders and movement restriction, as well as social distancing. Nevertheless, with the occurrence of the common variants of concern (VOCs), especially Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Southeast Asia is facing a significant increase in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Now, the area also has the threats of the spreading out of the dangerous variant - Omicron (B.1.1.529) from other close countries or regions. COVID-19 countermeasures such as closures and social distancing seem to be insufficient. Moreover, Southeast Asia is being held back by a shortage of vaccines and other medical resources. This work focuses on describing the COVID-19 situation, the virus variants, and the coverage of COVID-19 vaccination in the area. We also provide perspectives on the COVID-19 vaccine distribution, protecting the economic capitals, developing the green zone, and the importance of finding more vaccine supplies in Southeast Asia.

Predictive In Vitro-In Vivo Extrapolation for Time Dependent Inhibition of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 Using Pooled Human Hepatocytes, Human Liver Microsomes, and a Simple Mechanistic Static Model.

Inactivation of Cytochrome P450 (CYP450) enzymes can lead to significant increases in exposure of comedicants. The majority of reported in vitro to in vivo extrapolation (IVIVE) data have historically focused on CYP3A, leaving the assessment of other CYP isoforms insubstantial. To this end, the utility of human hepatocytes (HHEP) and human liver microsomes (HLM) to predict clinically relevant drug-drug interactions was investigated with a focus on CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Evaluation of IVIVE for CYP2B6 was limited to only weak inhibition. A search of the University of Washington Drug-Drug Interaction Database was conducted to identify a clinically relevant weak, moderate, and strong inhibitor for selective substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6, resulting in 18 inhibitors for in vitro characterization against 119 clinical interaction studies. Pooled human hepatocytes and HLM were preincubated with increasing concentrations of inhibitors for designated timepoints. Time dependent inhibition was detected in HLM for four moderate/strong inhibitors, suggesting that some optimization of incubation conditions (i.e., lower protein concentrations) is needed to capture weak inhibition. Clinical risk assessment was conducted by incorporating the in vitro derived kinetic parameters maximal rate of enzyme inactivation (min-1) (kinact) and concentration of inhibitor resulting in 50% of the maximum enzyme inactivation (KI) into static equations recommended by regulatory authorities. Significant overprediction was observed when applying the basic models recommended by regulatory agencies. Mechanistic static models, which consider the fraction of metabolism through the impacted enzyme, using the unbound hepatic inlet concentration lead to the best overall prediction accuracy with 92% and 85% of data from HHEPs and HLM, respectively, within twofold of the observed value. SIGNIFICANCE STATEMENT: Coupling time-dependent inactivation parameters derived from pooled human hepatocytes and human liver microsomes (HLM) with a mechanistic static model provides an easy and quantitatively accurate means to determine clinical drug-drug interaction risk from in vitro data. Optimization is needed to evaluate time-dependent inhibition (TDI) for weak and moderate inhibitors using HLM. Recommendations are made with respect to input parameters for in vitro to in vivo extrapolation (IVIVE) of TDI with non-CYP3A enzymes using available data from HLM and human hepatocytes.

Dental-craniofacial Characteristics of Southern Vietnamese People with Well-balanced Face on Cephalometric Films and Its Comparison with Caucasians and Northern Vietnamese Population.

OBJECTIVES: The objective of this study was to evaluate the dental-craniofacial measurements of the Southern Vietnamese people aged 18 to 25 with well-balanced face on cephalometric films. MATERIALS AND METHODS: This cross-sectional study included 60 cephalometric tracings of students (30 males, 30 females). The cephalometric measurements were made on 34 angles, 26 distances, and 4 ratios of skeletal, dental, and soft tissue cephalometric analysis. The mean and standard deviation (SD) of the dental-craniofacial measurements were calculated and compared among male and female subjects and with Caucasian and the Northern Vietnamese population. RESULTS: Among the Southern Vietnamese cephalometric tracing samples, the majority of the linear measurements were smaller in female than in male, while the angular and ratio measurements showed no significant difference. When compared with Caucasians, the cranial fossa lengths, the vertical facial heights, the lengths of maxilla and mandible, and the facial convexity of the Southern Vietnamese people were significantly smaller (P < 0.01), while the upper and lower incisors protrusion, and lip protrusion were larger (P < 0.01). The maxillary and mandibular protrusions, and mandibular rotational patterns were similar between these two groups. When compared with the Northern Vietnamese population, the mandibular plane angle and the upper and lower incisor protrusion of the Southern Vietnamese people were significantly larger (P < 0.05). CONCLUSIONS: The dental-craniofacial measurements of the Southern Vietnamese people were different among male and female, and different than those of Caucasians and Northern Vietnamese population. Such differences should be taken into account when considering orthodontic and orthognathic treatment strategies.

Tailoring chemical compositions of biodegradable mesoporous organosilica nanoparticles for controlled slow release of chemotherapeutic drug.

Biodegradable periodic mesoporous organosilica nanoparticles (B-PMO) are an outstanding nanocarrier due to their biodegradability and high drug load capacities. The present study describes a synthesis of a phenylene-containing tetrasulfide based B-PMO, named P4S. The incorporation of aromatic phenylene groups into the framework creates a strong interaction between nanoparticles (NPs) with aromatic rings in the cordycepin molecules. This results in the low release profile under various conditions. In addition, the replacement of this linker slowed the degradation of nanoparticles. The physicochemical properties of the nanoparticles are evaluated and compared with a biodegradable ethane-containing tetrasulfide based PMO and a non-degradable MCM-41. The biodegradability of P4S is also demonstrated in a reducing environment and the 100 nm spherical nanoparticles completely decomposed within 14 days. The porous structure of P4S has a high loading of hydrophilic cordycepin (approximately 731.52 mg g-1) with a slow releasing speed. The release rates of P4S NPs are significantly lower than other materials, such as liposomes, gelatin nanoparticles, and photo-crosslinked hyaluronic acid methacrylate hydrogels, in the same solution. This specific release behavior could guarantee drug therapeutic effects with minimum side-effects and optimized drug dosages. Most importantly, according to the in vitro cytotoxicity study, cordycepin-loaded P4S NPs could retain the toxicity against liver cancer cell (HepG2) while suppressed the cytotoxicity against normal cells (BAEC).

Functionalization of zirconium-based metal-organic frameworks for gas sensing applications.

The functionalization and incorporation of noble metals in metal-organic frameworks have been widely used as efficient methods to enhance their applicability. Herein, a sulfone-functionalized Zr-MOF framework labeled Zr-BPDC-SO2 (BPDC-SO2 =dibenzo[b,d]-thiophene-3,7-dicarboxylate 5,5-dioxide) and its Pd-embedded composite were efficiently synthesized by adjusting their functional groups. The obtained compounds were characterized to assess their potential for gas sensing applications. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, specific surface area measurements, and thermogravimetric analysis were employed to characterize the new sensor materials. The gas sensing properties of the novel functionalized sensor materials were systematically investigated under various temperature, concentration, and gas type conditions. Owing to the strong hydrogen bonds of the sulfonyl groups and Zr6 clusters in the framework with the hydroxyl groups of ethanol, Zr-BPDC-SO2 emerged as an effective sensor for ethanol detection. In addition, Pd@Zr-BPDC-SO2 exhibited efficient hydrogen sensing performance, in terms of sensor dynamics and response. More importantly, the material showed a higher sensing response to hydrogen than to other gases, highlighting the important role of Pd in the Zr-MOF-based hydrogen sensor. The results of the sensing tests carried out in this study highlight the promising potential of the present materials for practical gas monitoring applications.