Fabrication of injectable bone substitute loading porous simvastatin-loaded poly(lactic-co-glycolic acid) microspheres

An injectable bone substitute (IBS) with well-controlled release mechanism of simvastatin (SIM) was fabricated from SIM loaded-porous poly(lactic-co-glycolic acid) microspheres (PLGA MSs), biphasic calcium phosphates (BCP) and CaCO3 nano powder as the solid phase and gelatin, citric acid and hydroxypropyl methylcellulose as the liquid phase. The ratios of PLGA MSs and BCP were varied to obtain IBS with optimal mechanical properties, biocompatibility and bioactivity. In vitro test with MG-63 pre-osteoblast cells showed that IBS with higher amount of PLGA MSs yield better cell adhesion and proliferation. In vivo study on rabbit femoral defect also suggested that the IBS promoted osteogenesis

Machine Learning-Based Prediction of Drug-Drug Interactions for Histamine Antagonist Using Hybrid Chemical Features

The requesting of detailed information on new drugs including drug-drug interactions or targets is often unavailable and resource-intensive in assessing adverse drug events. To shorten the common evaluation process of drug-drug interactions, we present a machine learning framework-HAINI to predict DDI types for histamine antagonist drugs using simplified molecular-input line-entry systems (SMILES) combined with interaction features based on CYP450 group as inputs. The data used in our research consisted of approved drugs of histamine antagonists that are connected to 26,344 DDI pairs from the DrugBank database. Various classification algorithms such as Naive Bayes, Decision Tree, Random Forest, Logistic Regression, and XGBoost were used with 5-fold cross-validation to approach a large-scale DDIs prediction among histamine antagonist drugs. The prediction performance shows that our model outperformed previously published works on DDI prediction with the best precision of 0.788, a recall of 0.921, and an F1-score of 0.838 among 19 given DDIs types. An important finding of the study is that our prediction is based solely on the SMILES and CYP450 and thus can be applied at the early stage of drug development

Fabrication of silver nanoparticle-containing electrospun polycaprolactone membrane coated with chitosan oligosaccharides for skin wound care

An ideal wound dressing should have several qualities to protect the wound from infection and other adverse factors. This study aimed to fabricate a wound care membrane combining the two well-known bioactive agents silver nanoparticles (AgNPs) and chitosan oligosaccharides (COS). In specific, this multilayer membrane (PCL-Ag/POX/COS) consisted of (1) the electrospun basement layer of poly(ε-caprolactone) (PCL) and AgNPs; (2) the intermediate amphiphilic layer of PCL and poloxamer 407 (POX); and (3) the coating layer of COS and poly(N-vinyl pyrrolidone) (PVP). Several characterisation tests showed that the membrane was successfully coated with COS and owned suitable characteristics as a wound dressing, including proper tensile strength (more significant than the typical value of the skin), the hydrophilic and fluid-absorbable innermost surface, the waterproof outermost basement, vapour permeability, rapid COS release, and gradual AgNP release. In vitro experiments proved its haemostatic effect and antibacterial activities. Though its 100% extract solution reduced in vitro fibroblast viability, through the skin-defected mouse model experiment, PCL-Ag/POX/COS was compatible with the wound tissue and exhibited several positive effects on wound healing. In conclusion, PCL-Ag/POX/COS was proven for its potential for wound care, but it needs further investigations to allow translation from bench to bedside

In Vivo Study of the Antibacterial Chitosan/Polyvinyl Alcohol Loaded with Silver Nanoparticle Hydrogel for Wound Healing Applications

Silver nanoparticles have attracted great interests widely in medicine due to its great characteristics of antibacterial activity. In this research, the antibacterial activity and biocompatibility of a topical gel synthesized from polyvinyl alcohol, chitosan, and silver nanoparticles were studied. Hydrogels with different concentrations of silver nanoparticles (15 ppm, 30 ppm, and 60 ppm) were evaluated to compare their antibacterial activity, nanoparticles’ sizes, and in vivo behaviors. The resulted silver nanoparticles in the hydrogel were characterized by TEM showing the nanoparticles’ sizes less than 22 nm. The in vitro results prove that the antibacterial effects of all of the samples are satisfied. However, the in vivo results demonstrate the significant difference among different hydrogels in wound healing, where hydrogel with 30 ppm shows the best healing rate

Characterizations and Antibacterial Efficacy of Chitosan Oligomers Synthesized by Microwave-Assisted Hydrogen Peroxide Oxidative Depolymerization Method for Infectious Wound Applications

The use of naturally occurring materials with antibacterial properties has gained a great interest in infected wound management. Despite being an abundant resource in Vietnam, chitosan and its derivatives have not yet been intensively explored for their potential in such application. Here, we utilized a local chitosan source to synthesize chitosan oligomers (OCS) using hydrogen peroxide (H2O2) oxidation under the microwave irradiation method. The effects of H2O2 concentration on the physicochemical properties of OCS were investigated through molecular weight, degree of deacetylation, and heavy metal contamination for optimization of OCS formulation. Then, the antibacterial inhibition was examined; the minimum inhibitory concentration and minimum bactericidal concentration (MIC and MBC) of OCS-based materials were determined against common skin-inhabitant pathogens. The results show that the local Vietnamese chitosan and its derivative OCS possessed high-yield purification while the molecular weight of OCS was inversely proportional and proportional to the concentration of H2O2, respectively. Further, the MIC and MBC of OCS ranged from 3.75 to less than 15 mg/mL and 7.5–15 mg/mL, respectively. Thus, OCS-based materials induce excellent antimicrobial properties and can be attractive for wound dressings and require further investigation

Optimization of Oligomer Chitosan/Polyvinylpyrrolidone Coating for Enhancing Antibacterial, Hemostatic Effects and Biocompatibility of Nanofibrous Wound Dressing

A synergistic multilayer membrane design is necessary to satisfy a multitude of requirements of an ideal wound dressing. In this study, trilayer dressings with asymmetric wettability, composed of electrospun polycaprolactone (PCL) base membranes coated with oligomer chitosan (COS) in various concentrations of polyvinylpyrrolidone (PVP), are fabricated for wound dressing application. The membranes are expected to synergize the hygroscopic, antibacterial, hemostatic, and biocompatible properties of PCL and COS. The wound dressing was coated by spraying the solution of 3% COS and 6% PVP on the PCL base membrane (PVP6–3) three times, which shows good interaction with biological subjects, including bacterial strains and blood components. PVP6–3 samples confirm the diameter of inhibition zones of 20.0 ± 2.5 and 17.9 ± 2.5 mm against Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The membrane induces hemostasis with a blood clotting index of 74% after 5 min of contact. In the mice model, wounds treated with PVP6–3 closed 95% of the area after 10 days. Histological study determines the progression of skin regeneration with the construction of granulation tissue, new vascular systems, and hair follicles. Furthermore, the newly-growth skin shares structural resemblances to that of native tissue. This study suggests a simple approach to a multi-purpose wound dressing for clinical treatment

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990–2021 : a systematic analysis from the Global Burden of Disease Study 2021

Background Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020–21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325–364) incident episodes of LRI, or 4350 episodes (4120–4610) per 100 000 population, and 2·18 million deaths (1·98–2·36), or 27·7 deaths (25·1–29·9) per 100 000. 502 000 deaths (406 000–611 000) were in children younger than 5 years, among which 254 000 deaths (197 000–320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1–104·0) episodes and 505 000 deaths (454 000–555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6–49·3] episodes) and Mycoplasma spp (25·3 million [23·5–27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000–459 000]) and K pneumoniae (176 000 [158 000–194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9–46·9), from 56·5 deaths (51·3–61·9) to 32·9 deaths (29·9–35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1–18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8–78·9) decline in the number of influenza deaths and a 66·7% (56·6–75·3) decline in the number of RSV deaths. Interpretation Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK)