Metabolic Reprogramming of Macrophages by Biomimetic Melatonin-Loaded Liposomes Effectively Attenuates Acute Gouty Arthritis in a Mouse Model.

Gouty arthritis is characterized by an acute inflammatory response triggered by monosodium urate (MSU) crystals deposited in the joints and periarticular tissues. Current treatments bring little effects owing to serious side effects, necessitating the exploration of new and safer therapeutic options. Macrophages play a critical role in the initiation, progression, and resolution of acute gout, with the cellular profiles closely linked to their activation and polarization.

Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization.

Although deubiquitinases (DUBs) have been well described in liver tumorigenesis, their potential roles and mechanisms have not been fully understood. In this study, we identified ubiquitin-specific protease 1 (USP1) as an oncogene with essential roles during hepatocellular carcinoma (HCC) progression. USP1, with elevated expression levels and clinical significance, was identified as a hub DUB for HCC in multiple bioinformatics datasets.

An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses.

Marrow niches in osteosarcoma (OS) are a specialized microenvironment that is essential for the maintenance and regulation of OS cells. However, existing animal xenograft models are plagued by variability, complexity, and high cost. Herein, we used a decellularized osteosarcoma extracellular matrix (dOsEM) loaded with extracellular vesicles from human bone marrow-derived stem cells (hBMSC-EVs) and OS cells as a bioink to construct a micro-osteosarcoma (micro-OS) through 3D printing.

Smart Targeted Delivery Systems for Enhancing Antitumor Therapy of Active Ingredients in Traditional Chinese Medicine.

As a therapeutic tool inherited for thousands of years, traditional Chinese medicine (TCM) exhibits superiority in tumor therapy. The antitumor active components of TCM not only have multi-target treatment modes but can also synergistically interfere with tumor growth compared to traditional chemotherapeutics. However, most antitumor active components of TCM have the characteristics of poor solubility, high toxicity, and side effects, which are often limited in clinical application.

The design and straightforward synthesis of multifunctional DNA microgels for the improved targeted delivery of antitumor drugs.

Multifunctional drug delivery platforms represent ideal approaches to reliably targeting pharmacological agents of interest to the complex tumor microenvironment (TME), yet the complicated synthesis processes, high costs, and toxicities associated with these agents have hindered their clinical application to date. In this study, the properties of the TME are leveraged to develop a multifunctional pNAB/AS DNA microgel that is able to actively target tumors. This microgel is generated by a straightforward one-step free radical precipitation polymerization procedure, exhibiting extremely high drug encapsulation efficiency (∼90%), and is responsive to three environmental stimuli including temperature, reduction, and an acidic pH while showing minimal drug leakage under physiological conditions.

Microneedle-Assisted Topical Delivery of Idebenone-Loaded Bioadhesive Nanoparticles Protect against UV-Induced Skin Damage.

Ultraviolet (UV) radiation can penetrate the basal layer of the skin and induce profound alterations in the underlying dermal tissues, including skin pigmentation, oxidative stress, photoaging, glycation, and skin cancer. Idebenone (IDB), an effective antioxidant that suppresses melanin biosynthesis and glycation, can protect the skin from UV-induced damage, accounting for its use in commercial anti-aging formulations. Ideally, IDB formulations should retain IDB inside the skin for a sufficient period, despite disturbances such as sweating or swimming.

Dual-drug codelivery nanosystems: An emerging approach for overcoming cancer multidrug resistance.

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy.

The relationship between transthoracic echocardiography and mortality in adult patients with multiple organ dysfunction syndrome: analysis of the MIMIC-III database.

Background: For patients with multiple organ dysfunction syndrome (MODS), timely assessment of the condition and real-time adjustment of the treatment plan are of critical importance. To this end, transthoracic echocardiography (TTE) is widely used in clinical practice, but whether TTE can improve the short-term prognosis of MODS patients is currently unclear.

Methods: We extracted data of patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database and included cases according to inclusion and exclusion criteria.

A novel artificial intelligence protocol to investigate potential leads for diabetes mellitus.

Dipeptidyl peptidase-4 (DPP4) is highly participated in regulating diabetes mellitus (DM), and inhibitors of DPP4 may act as potential DM drugs. Therefore, we performed a novel artificial intelligence (AI) protocol to screen and validate the potential inhibitors from Traditional Chinese Medicine Database. The potent top 10 compounds were selected as candidates by Dock Score.

A novel artificial intelligence protocol to investigate potential leads for Parkinson's disease.

Previous studies have shown that small molecule inhibitors of NLRP3 may be a potential treatment for Parkinson's disease (PD). NACHT, LRR and PYD domains-containing protein 3 (NLRP3), heat shock protein HSP 90-beta (HSP90AB1), caspase-1 (CASP1) and cellular tumor antigen p53 (TP53) have significant involvement in the pathogenesis pathway of PD. Molecular docking was used to screen the traditional Chinese medicine database TCM Database@Taiwan.

A novel artificial intelligence protocol for finding potential inhibitors of acute myeloid leukemia.

There is currently no effective treatment for acute myeloid leukemia, and surgery is also ineffective as an important treatment for most tumors. Rapidly developing artificial intelligence technology can be applied to different aspects of drug development, and it plays a key role in drug discovery. Based on network pharmacology and virtual screening, candidates were selected from the molecular database.

(R)-2-Phenyl-4,5-Dihydrothiazole-4-Carboxamide Derivatives Containing a Diacylhydrazine Group: Synthesis, Biological Evaluation, and SARs.

A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, H NMR, C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated.