Pleiotropic Multi-Drug Co-Assembled Nanocomposites Offer Protection Against Doxorubicin-Induced Cardiotoxicity.

Background: Doxorubicin (DOX) is a first-line chemotherapeutic agent, yet its clinical utility is limited by doxorubicin-induced cardiotoxicity (DIC), a dose-dependent side effect. Current drug delivery strategies fail to prevent off-target accumulation of DOX in cardiac tissue, necessitating innovative therapeutic approaches that protect the heart without compromising antitumor efficacy through targeted cardioprotection.

Methods: We developed a multifunctional self-assembled nanoplatform (PGPP/NPs) via co-assembly of ginsenoside Rb1, probucol (PB), and a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (PI), with surface modification using PCM peptide for cardiomyocyte-targeted delivery.

Biomimetic Ginsenoside Rb1 and Probucol Co-Assembled Nanoparticles for Targeted Atherosclerosis Therapy via Inhibition of Oxidative Stress, Inflammation, and Lipid Deposition.

To overcome the limitations of conventional oral drugs and nanocarrier-dependent delivery systems in atherosclerosis (AS) therapy, our work proposes an "integration of Chinese and Western medicine" approach to develop a new biomimetic traditional Chinese and Western medicine components coassembled nanoparticles (NPs), termed as MMVs/RPNPs, for targeted AS therapy. In this work, we demonstrated that ginsenoside Rb1 can coassemble with probucol without excipients to form stable carrier-free NPs, termed RPNPs. To impart the specific targeting property to atherosclerotic sites, macrophage microvesicles (MMVs) were utilized to coat the RPNPs to obtain the MMVs/RPNPs.

A polymerized probucol nanoformulation with neutrophil extracellular vesicle camouflage for cerebral ischemia-reperfusion injury therapy.

This study leverages the unique advantages of polyprodrug systems and biomimetic technology to develop a novel biomimetic nanoformulation, in which neutrophil extracellular vesicles (NEVs) are coated onto reactive oxygen species (ROS)-sensitive probucol-based polyprodrug nanoparticles (NPPBNPs). This NEV-camouflaged biomimetic nanoformulation holds significant potential for the effective treatment of cerebral ischemia-reperfusion injury (CIRI), offering multifaceted therapeutic effects, such as ROS elimination, inhibition of oxidative stress-induced neuronal apoptosis, attenuation of glial hyperactivation, and suppression of pro-inflammatory mediator secretion. In a murine CIRI model, NPPBNPs markedly enhanced neuronal viability, ameliorated the ischemic penumbra, restored behavioral functions, and exhibited an acceptable safety profile.

A Carrier-Free Triple-Drug Co-Assembled Nanoformulation for Synergistic Treatment of Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia-reperfusion injury (CIRI), a critical complication arising from the recanalization of blood flow to the ischemic region of the brain following an ischemic stroke, poses significant challenges in clinical management due to the lack of efficacious therapeutic interventions. This condition markedly impacts the patient prognosis and quality of life. Herein, we developed a carrier-free triple-drug co-assembled nanoformulation, designated as SRPNNPs, to achieve safe and efficient treatment of CIRI.

Nonalcoholic Fatty Liver Disease: Changes in Gut Microbiota and Blood Lipids.

Background And Aims: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing.

Methods: Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed.

Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress.

Background: Hepatic fibrosis is a common pathological process in many chronic liver diseases. TXNDC5 has been shown to be involved in the progression of renal and pulmonary fibrosis. However, the role of TXNDC5 in hepatic fibrosis is unknown.

Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.

Purpose: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML.

Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic and progressive inflammation of the synovium. Focused ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness; however, it remains unclear which immune subsets respond to ultrasound stimulation. In this study, we showed that spleen-targeted low-frequency pulsed focused ultrasound (LFPFU) effectively improved the severity of arthritis in an arthritis mouse model established in DBA/1J mice.

Knockdown of ARL5B Induces Mitochondrial-mediated Apoptosis and Inhibits Glycolysis in Breast Cancer Cells by Activating MDA5 Signaling.

Aim: Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells.

Background: ADP-ribosylation factor-like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and breast cancer (BC) progression, but the underlying mechanism needs to be further understood.

Objective: We investigated the effects of ARL5B on the apoptosis and glycolysis of breast cancer cells and its underlying mechanisms.

Elastography for the differential diagnosis of malignant versus benign testicular lesions: a meta-analysis.

Purpose: The aim of this study was to evaluate the value of elastography in the differential diagnosis of benign versus malignant testicular lesions.

Methods: The PubMed, Cochrane Library, and Embase databases were searched for relevant studies. The diagnostic accuracy of elastography was evaluated using pooled sensitivity, specificity, likelihood ratio, post-test probability, diagnostic odds ratio, and by summarizing the area under the hierarchical summary receiver operating characteristic (HSROC) curve.

One step further into the blackbox: a pilot study of how to build more confidence around an AI-based decision system of breast nodule assessment in 2D ultrasound.

Objectives: To investigate how a DL model makes decisions in lesion classification with a newly defined region of evidence (ROE) by incorporating "explainable AI" (xAI) techniques.

Methods: A data set of 785 2D breast ultrasound images acquired from 367 females. The DenseNet-121 was used to classify whether the lesion is benign or malignant.

The role of grey-scale ultrasound in the diagnosis of adhesive capsulitis of the shoulder: a systematic review and meta-analysis.

Aims: In this systematic review and meta-analysis, we discuss the value of grey-scale ultrasonography (US) in diagnosing adhesive capsulitis of the shoulder (ACS).

Material And Methods: We retrieved relevant studies from PubMed, Cochrane Library, and Embase before 8 April 2019. We selected 7 studies concerning 446 patients (490 shoulders) that used grey-scale US to diagnose ACS and magnetic resonance imaging (MRI) or arthroscopy as the reference standard.

Short-term numerosity training promotes symbolic arithmetic in children with developmental dyscalculia: The mediating role of visual form perception.

Studies have shown that numerosity-based arithmetic training can promote arithmetic learning in typically developing children as well as children with developmental dyscalculia (DD), but the cognitive mechanism underlying this training effect remains unclear. The main aim of the current study was to examine the role of visual form perception in arithmetic improvement through an 8-day numerosity training for DD children. Eighty DD children were selected from four Chinese primary schools.

Visual form perception is fundamental for both reading comprehension and arithmetic computation.

Visual perception has been found to be a critical factor for reading comprehension and arithmetic computation in separate lines of research with different measures of visual form perception. The current study of 1099 Chinese elementary school students investigated whether the same visual form perception (assessed by a geometric figure matching task) underlies both reading comprehension and arithmetic computation. The results showed that visual form perception had close relations with both reading comprehension and arithmetic computation, even after controlling for age, gender, and cognitive factors such as processing speed, attention, working memory, visuo-spatial processing, and general intelligence.

Diffusion Kurtosis Imaging Detects Microstructural Changes in the Brain after Acute Alcohol Intoxication in Rats.

The aim of this study was to test the technical feasibility of diffusion kurtosis imaging (DKI) in the brain after acute alcohol intoxication. Diffusion tensor imaging (DTI) and DKI during 7.0 T MRI were performed in the frontal lobe and thalamus before and 30 min, 2 h, and 6 h after ethyl alcohol administration.