Ultrasound-Guided Percutaneous Microwave Coagulation Studies on VX2 Rabbit Models for Breast Cancer Treatment and Ultrasound Imaging Assessment.

Background: The study aimed to explore the tissue morphology and hemodynamics of rabbit VX2 breast carcinoma by high-frequency ultrasound (US) and the effectiveness and safety of US-guided percutaneous microwave coagulation (PMC) therapy on rabbit VX2 breast tumors.

Methods: Twenty VX2 tumor-bearing rabbits were assessed using color Doppler ultrasound for tumor growth characteristics including echo, size, blood supply and hemodynamic parameters once a week for six weeks. Subsequently, US-guided PMC was performed in randomly assigned ten VX2 tumor-bearing rabbits (the other ten as controls).

Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain.

Sensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs.

Endothelial FOXM1 and Dab2 promote diabetic wound healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor-dependent (VEGF-dependent) angiogenesis remain unclear. In our study, the molecular underpinnings of endothelial dysfunction in diabetes are investigated, focusing on the roles of disabled-2 (Dab2) and Forkhead box M1 (FOXM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high-glucose-treated primary mouse skin endothelial cells.

FOXM1 promotes malignant biological behavior and metabolic reprogramming by targeting SPINK1 in hepatocellular carcinoma and affecting the p53 pathway.

This study investigates the role of SPINK1 in liver cancer and its regulatory relationship with FOXM1. Using differential gene analysis in the GEO database, SPINK1 was identified as overexpressed in liver cancer tissues and associated with poor prognosis, confirmed via PCR. Functional assays demonstrated that SPINK1 knockdown reduced proliferation, migration, and invasion in liver cancer cells, while promoting apoptosis.

Hydrogel doped with sinomenine-CeO nanoparticles for sustained intra-articular therapy in knee osteoarthritis.

In this study, we developed an intra-articular injectable hydrogel drug depot (SMN-CeO@G) for sustained OA treatment. This hydrogel system, which carries sinomenine-loaded cerium dioxide nanoparticles (SMN-CeO), enhances anti-inflammatory and anti-apoptotic effects within the joint cavity. SMN-CeO@G features a three-dimensional network structure with an approximate pore size of 10 μm, stably encapsulating SMN-CeO nanoparticles (∼75 nm).

A long-term follow-up study of gastric peroral endoscopic myotomy (G-POEM) in a large cohort of patients with postsurgical gastroparesis.

Introduction: Postoperative gastroparesis occurs after surgeries which affect the upper digestive tract. Gastric peroral endoscopic myotomy (G-POEM) is a treatment for postoperative gastroparesis. The present study boasts the long-term efficacy and safety of G-POEM in a large cohort of patients.

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus.

Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis.

Rationale: Low density cholesterol receptor (LDLR) in the liver is critical for the clearance of low-density lipoprotein cholesterol (LDL-C) in the blood. In atherogenic conditions, proprotein convertase subtilisin/kexin 9 (PCSK9) secreted by the liver, in a nonenzymatic fashion, binds to LDLR on the surface of hepatocytes, preventing its recycling and enhancing its degradation in lysosomes, resulting in reduced LDL-C clearance. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity.

Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution.

Macrophage efferocytosis prevents apoptotic cell (AC) accumulation and triggers inflammation-resolution pathways. The mechanisms linking efferocytosis to resolution often involve changes in macrophage metabolism, but many gaps remain in our understanding of these processes. We now report that efferocytosis triggers an indoleamine 2,3-dioxygenase-1 (IDO1)-dependent tryptophan (Trp) metabolism pathway that promotes several key resolution processes, including the induction of pro-resolving proteins, such interleukin-10, and further enhancement of efferocytosis.

The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma.

Objective: This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC).

Methods: The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed.

The effect of internal orifice narrowing in laparoscopic inguinoscrotal hernia repair to prevent seroma formation: a prospective double-blind randomized controlled trial.

Objectives: Seroma represents the most prevalent postoperative complication following laparoscopic inguinal hernia repair, particularly in the case of large inguinoscrotal hernias. This randomized controlled trial was undertaken with the objective of assessing the effects of internal orifice narrowing achieved by suturing the divided distal hernia sac in laparoscopic repair of indirect inguinoscrotal hernias.

Methods: A total of 58 patients aged 18 years or older, were randomized into two groups: Group I, which underwent internal orifice narrowing, and Group II, which served as the control without narrowing.

Diagnostic value of measuring the talofibular space using stress sonography in chronic lateral ankle instability.

Objectives: To investigate the diagnostic value of measuring the talofibular space using stress sonography for chronic lateral ankle instability (CLAI).

Materials & Methods: We recruited patients who were clinically diagnosed with CLAI between October 2018 and December 2019 (CLAI group). A control group of healthy volunteers was also included for this study.

Stimuli-Responsive Nanotechnology for RNA Delivery.

Ribonucleic acid (RNA) drugs have shown promising therapeutic effects for various diseases in clinical and preclinical studies, owing to their capability to regulate the expression of genes of interest or control protein synthesis. Different strategies, such as chemical modification, ligand conjugation, and nanotechnology, have contributed to the successful clinical translation of RNA medicine, including small interfering RNA (siRNA) for gene silencing and messenger RNA (mRNA) for vaccine development. Among these, nanotechnology can protect RNAs from enzymatic degradation, increase cellular uptake and cytosolic transportation, prolong systemic circulation, and improve tissue/cell targeting.

Bioengineered nanotechnology for nucleic acid delivery.

Nucleic acid-based therapy has emerged as a promising therapeutic approach for treating various diseases, such as genetic disorders, cancers, and viral infections. Diverse nucleic acid delivery systems have been reported, and some, including lipid nanoparticles, have exhibited clinical success. In parallel, bioengineered nucleic acid delivery nanocarriers have also gained significant attention due to their flexible functional design and excellent biocompatibility.

Comparing the effectiveness of extracorporeal shockwave therapy and myofascial release therapy in chronic pelvic pain syndrome: study protocol for a randomized controlled trial.

Background: Chronic prostatitis/chronic pelvic pain syndrome is a highly prevalent syndrome. Previous studies showed that extracorporeal shockwave therapy and myofascial release therapy could improve the quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Theoretically, combined therapy with extracorporeal shockwave therapy and myofascial release therapy will likely have significant advantages in treating CP/CPPS.

'Passive' nanoparticles for organ-selective systemic delivery: design, mechanism and perspective.

Nanotechnology has shown tremendous success in the drug delivery field for more effective and safer therapy, and has recently enabled the clinical approval of RNA medicine, a new class of therapeutics. Various nanoparticle strategies have been developed to improve the systemic delivery of therapeutics, among which surface modification of targeting ligands on nanoparticles has been widely explored for 'active' delivery to a specific organ or diseased tissue. Meanwhile, compelling evidence has recently been reported that organ-selective targeting may also be achievable by systemic administration of nanoparticles without surface ligand modification.

ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy.

Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment.

Hydrogels for RNA delivery.

RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy.

Targeting Epsins to Inhibit Fibroblast Growth Factor Signaling While Potentiating Transforming Growth Factor-β Signaling Constrains Endothelial-to-Mesenchymal Transition in Atherosclerosis.

Background: Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, the underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) in atherosclerosis and assessed the efficacy of a therapeutic peptide in a preclinical model of this disease.

Methods: Using single-cell RNA sequencing combined with molecular, cellular, and biochemical analyses, we investigated the role of epsins in stimulating EndoMT using knockout in and lineage tracing/proprotein convertase subtilisin/kexin type 9 serine protease mutant viral-induced atherosclerotic mouse models.

Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.

The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (T17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T17-cell-mediated anti-tumour responses.