The recent applications of nanotechnology in the diagnosis and treatment of common cardiovascular diseases.

Almost a third of all fatalities may be attributed to cardiovascular disease (CVD), making it a primary cause of mortalities worldwide. Better diagnostic tools and secure, non-invasive imaging techniques are needed to offer accurate information on CVD progression. Several elements contribute to the success of CVD personalized therapy, and two of the most crucial are accurate diagnosis and early detection. The therapy options available for conditions with a pathogenesis that unfold over decades, such as CVD, are very condition-specific and disease-stage based. Nanotechnology is increasingly being used as a therapeutic tool in the biomedical area, where they are used in various contexts, including diagnostics, biosensing, and drug administration. This review article provides an overview of the most recent applications of nanotechnology in the detection and management of prevalent CVDs.

Sex-specific effects of excipients on oral drug bioavailability.

The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.

Identification of a novel sepsis prognosis model and analysis of possible drug application prospects: Based on scRNA-seq and RNA-seq data.

Sepsis is a disease with a high morbidity and mortality rate. At present, there is a lack of ideal biomarker prognostic models for sepsis and promising studies using prognostic models to predict and guide the clinical use of medications. In this study, 71 differentially expressed genes (DEGs) were obtained by analyzing single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq data, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were performed on these genes. Then, a prognosis model with CCL5, HBD, IFR2BP2, LTB, and WFDC1 as prognostic signatures was successfully constructed after univariate LASSO regression analysis and multivariate Cox regression analysis. Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) time curve analysis, internal validation, and principal component analysis (PCA) further validated the model for its high stability and predictive power. Furthermore, based on a risk prediction model, gene set enrichment analysis (GSEA) showed that multiple cellular functions and immune function signaling pathways were significantly different between the high- and low-risk groups. In-depth analysis of the distribution of immune cells in healthy individuals and sepsis patients using scRNA-seq data revealed immunosuppression in sepsis patients and differences in the abundance of immune cells between the high- and low-risk groups. Finally, the genetic targets of immunosuppression-related drugs were used to accurately predict the potential use of clinical agents in high-risk patients with sepsis.

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment.

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

Sex-specific and concentration-dependent influence of Cremophor RH 40 on ampicillin absorption via its effect on intestinal membrane transporters in rats.

Pharmaceutical excipients are the basic materials and important components of pharmaceutical preparations, and play an important role in improving the efficacy of drugs and reducing adverse reactions. Therefore, selecting suitable excipients for dosage form is an important step in formulation development. An increasing number of studies have revealed that the traditionally regarded "inert" excipients can, however, influence the bioavailability of drugs. Moreover, these effects on the bioavailability of drugs caused by pharmaceutical excipients may differ in between males and females. In this study, the in situ effect of the widely-used pharmaceutical excipient Cremophor RH 40 spanning from 0.001% to 0.1% on the intestinal absorption of ampicillin in male and female rats using closed-loop models was investigated. Cremophor RH 40 ranging from 0.03% to 0.07% increased the absorption of ampicillin in females, however, was decreased in male rats. The mechanism of such an effect on drug absorption is suggested to be due to the interaction between Cremophor RH 40 and two main membrane transporters P-gp and PepT1. Cremophor RH 40 altered the PepT1 protein content in a sex-dependent manner, showing an increase in female rats but a decrease in males. No modification on the PepT1 mRNA abundance was found with Cremophor RH 40, indicating that the excipient may regulate the protein recruitment of the plasma membrane from the preformed cytoplasm pool to alter the PepT1 function. This influence, however, may differ between males and females. As such, the study herein shows that supposedly inert excipient Cremophor RH 40 can influence membrane fluidity, uptake and efflux transporters in a sex- and concentration-dependent manner. These findings, therefore, highlight the need for sex-specific studies in the application of solubilizing excipients in drug formulation development.

Brain-Inspired Experience Reinforcement Model for Bin Packing in Varying Environments.

Bin-packing problem (BPP) is a typical combinatorial optimization problem whose decision-making process is NP-hard. This article examines BPPs in varying environments, where random number and shape of items are to be packed in different instances. The objective is to find a unified model to derive optimal decision process that maximizes the utilization of bins. To this end, by mimicking the experience-based reasoning process of humans, this article proposes a novel brain-inspired experience reinforcement model, which takes advantage of both biological and engineering systems. By learning experience from similar situations, the model is adaptive, such as the human brain for sophisticated scenarios and varying environments. The proposed model mimics the functional coordination among brain regions by knowledge representation and knowledge extraction modules. The former one corresponds to the part of information processing and experience storage. The latter one includes two parts that can train reasoning strategies and improve the decision performance. The proposed model is applied to instances of random number and shape of items of BPP. The obtained results outperform the state-of-the-art methods for BPPs in varying environments.

Inferring Centrality from Network Snapshots.

The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data.

A comparison of clinical outcomes for implants placed in fresh extraction sockets versus healed sites in periodontally compromised patients: a 1-year follow-up report.

PURPOSE: The aim of this 1-year prospective study was to evaluate, in patients with severe periodontitis, the clinical performance of implants placed immediately after extraction of remaining teeth or in healed sockets and immediately loaded for prosthetic oral rehabilitation, and to compare the clinical outcomes for implants placed in fresh extraction sockets versus healed sites. MATERIALS AND METHODS: All patients in this study had received periodontal treatment; however, the teeth were eventually deemed hopeless. The remaining teeth were extracted, the periodontally compromised sites were debrided, implants were inserted guided by a surgical template, and a provisional restoration was delivered immediately. The opposing arch was restored with a complete denture. Definitive prostheses were inserted after 6 months. Initial implant and prosthesis stability and the inflammatory response were evaluated. Clinical and radiographic analyses were performed. RESULTS: A total of 84 rough-surfaced implants were placed (50 in the maxilla and 34 in the mandible). Of these, 32 were placed in fresh extraction sockets. Four implants in three patients failed within the first 6 months, resulting in an implant survival rate of 95.2%. All of the failed implants had been placed in fresh maxillary extraction sockets. The survival rates were 92% (46/50) in the maxilla and 100% (34/34) in the mandible. Prosthetic success was 100%. The mean bone level change (± SE) between baseline and 12 months was -1.12 ± 0.18 mm. There were no statistically significant differences in insertion torque and alveolar bone loss between postextraction sites and healed sites. CONCLUSIONS: The implant failure rate was higher in maxillary postextraction sites. This indicates a heightened risk of failure for immediate implants placed in periodontally compromised maxillae. Nevertheless, a satisfactory prosthetic success was achieved after 1 year.