Sodium hyaluronate-modified Fe-shikonin self-assembly nanoparticle for effective tumor therapy and reduced tumor metastasis.

Tumor metastasis constitutes a major obstacle in cancer treatment and affects patients' quality of life. In this study, we synthesized Fe-shikonin nanoparticles (SF NPs) through a one-step self-assembly process utilizing shikonin (SK) and Fe. Following the synthesis of nanoparticles, the challenges associated with the poor water solubility and the low bioavailability of SK, as well as its toxicity and adverse effects on normal tissues, could be addressed, thereby enhancing its applicability.

Endosialin promotes vascular maturation by inhibiting Cyr61 expression in melanoma metastasis.

Background: Extensive tumor cell metastasis is associated with poor patient prognosis. Tumor endothelial cells demonstrate distinct proangiogenic phenotypes compared to normal endothelial cells, partially mediated by pericyte-derived secreted factors. Endosialin, a pericyte biomarker implicated in vascular maturation and metastatic progression, remains mechanistically undefined in this context.

Self-Delivery Nanotherapeutics for Tumor Low-Temperature Photothermal Immunotherapy through Cascade Heat Shock Protein and Inflammation Inhibition.

The clinical efficacy of immunotherapy in triple-negative breast cancer (TNBC) faces dual barriers: poor immunogenicity and a suppressive tumor microenvironment. While low-temperature photothermal therapy (LTPTT) has emerged as a potential immunostimulatory strategy, its efficacy is counteracted by heat shock protein (HSP) induction and COX-2/PGE2-mediated immunosuppression. To address these challenges, we developed a multifunctional immunophotothermal nanoplatform (IAC NPs) through rational engineering of human serum albumin for combinatorial delivery of indocyanine green as a photothermal converter, atovaquone for HSP70-mediated thermoresistance blockade, and celecoxib for COX-2/PGE2 pathway inhibition.

Bioequivalence of two doxorubicin liposome formulations (LY01612 and Caelyx) using free and encapsulated doxorubicin concentrations in Chinese patients with advanced breast cancer.

Objective: To determine the pharmacokinetic properties and bioequivalence of a reference doxorubicin injectable formulation (Caelyx) and the test formulation, a newly developed doxorubicin hydrochloride liposome injection formulation (LY01612), administered as single bolus doses in Chinese patients with advanced breast cancer.

Materials And Methods: The study was multicentric, randomized, open-label, two-treatment, two-period, two-sequence, single dose with crossover. The dose, equivalent to 50 mg/m, was administered intravenously on the first day of each 28-day treatment period.

Multi-Target Inhibitor of ZJQ- 3 F Against AChE/BACE1/GSK3β Targets Improves the Cognitive Impairment of APP/PS1/Tau Triple-Transgenic Mouse Models of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a multifactorial neuropathology characterized by the accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs) and cholinergic system dysfunction. At present, there is no effective treatment strategy for AD. Our previous research showed that ZJQ-3F acts as an inhibitor of AChE/BACE1/GSK3β, and showed good blood-brain barrier permeability, appropriate bioavailability and oral safety.

All-In-One Gadolinium-Doxorubicin Nanoassemblies for Spatial Delivery and Chemoresistance Reversal in Tumor Microenvironments.

Efficiently overcoming chemoresistance in tumor microenvironments remains a critical hurdle in cancer therapy due to tumor heterogeneity, limited drug penetration, and adaptive resistance mechanisms. Herein, we report the design and application of all-in-one gadolinium-doxorubicin nanoassemblies (GDNAs) for spatially targeted delivery and chemoresistance reversal. These multifunctional nanoassemblies integrate a lanthanide-based component for real-time imaging and doxorubicin for chemotherapy, coupled with bioinformatics-guided small interfering RNAs (siRNAs) to silence key resistance-associated genes such as BCL2 and BIRC5.

Self-assembled metal-coordinated nanoparticles for synergistic energy metabolism inhibition and low-temperature photothermal therapy.

Photothermal therapy has been observed to upregulate the heat shock protein 70 (HSP 70) expression in tumor cells, consequently diminishing the anti-tumor efficacy of the treatment. The expression of HSP 70 is intricately linked to the adenosine triphosphate (ATP) levels within tumors, suggesting that modulating energy metabolism could potentially enhance the effectiveness of photothermal therapy. To address these challenges, ATO-QUE-Fe-PVP K30 nanoparticles (AQFP NPs) were synthesized through the coordinated self-assembly of the oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO) and the glycolysis inhibitor quercetin (QUE) with ferrous ions (Fe) for synergetic energy depletion and low-temperature photothermal therapy (LTPTT).

Engineering a Self-Delivery Nanoplatform for Chemo-Photodynamic-Immune Synergistic Therapies against Aggressive Melanoma.

The effectiveness of immunotherapy in killing melanoma is hindered by a T-cell deficiency and the lack of tumor immunogenicity. Consequently, there is an urgent need for a platform that can further activate the immune system and boost the immune response of the host to tumors. Compared with monotherapy, combination therapy shows promise in improving treatment efficacy and response rates.

In situ generation of Copper sulfide within Poly(lactic-co-glycolic acid): A strategy for Safer photothermal therapy in Triple-Negative breast cancer.

Copper sulfide nanoparticles (CuS NPs) have garnered significant attention in photothermal therapy (PTT) owing to their facile synthesis, biodegradability, stability, and excellent photothermal conversion efficiency. Nonetheless, their potential toxic effects have restricted their application. This research focuses on the encapsulation of CuS NPs with the biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) to enhance their biocompatibility, thereby improving the efficacy and safety of PTT in the treatment of triple-negative breast cancer (TNBC).

A Self-Amplifying Photodynamic Biomedicine for Cascade Immune Activation Against Triple-Negative Breast Cancer.

The efficacy of immunotherapy in triple-negative breast cancer (TNBC) is significantly hindered by its low immunogenicity and immunosuppressive tumor microenvironment. Non-invasive photodynamic therapy (PDT) is increasingly recognized as a potential immunotherapeutic stimulant in the treatment of TNBC. However, photodynamic immunotherapy is constrained by tumor hypoxia and excessive inflammation suppression during the course of treatment.

Big-five personality traits and depression: chain mediation of self-efficacy and walking.

Background: Depression is a major global public health concern, with research indicating a correlation between personality traits and depression. This study aimed to explore the potential mediating roles of self-efficacy and walking in the relationship between personality traits and depression among Chinese residents.

Methods: A cross-sectional questionnaire survey was conducted from July 10 to September 15, 2021, involving 11,031 Chinese residents across 23 provinces, 5 autonomous regions, and 4 municipalities Participants provided data on demographics, personality traits (using the Ten-Item Personality Inventory), self-efficacy (using the New General Self-Efficacy Scale), chronic disease self-management (using the Chronic Disease Self-Management Study Measures), and depression (using the Patient Health Questionnaire-9).

Tumor-Targeted Metal-Organic Framework for Improved Photodynamic Therapy and Inhibited Tumor Metastasis in Melanoma.

Tumor hypoxia and elevated intracellular glutathione (GSH) levels significantly compromise the effectiveness of photodynamic therapy (PDT) in treating melanoma. In this study, we synthesized positively charged nanoparticles through a self-assembly method, incorporating photosensitizer verteporfin (VER), mitochondrial respiratory inhibitor atovaquone (ATO), and Fe. Subsequently, the nanoparticles were modified with sodium hyaluronate (HA) to obtain HA-ATO-Fe-VER nanoparticles (HAFV NPs).

Development of FK506-loaded maleimide-functionalized cationic niosomes for prolonged retention and therapeutic efficacy in dry eye disease.

Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy.

Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.

Background: Nivolumab (Opdivo) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.

Objectives: This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo) in healthy Chinese male subjects.

Endosialin-positive CAFs promote hepatocellular carcinoma progression by suppressing CD8 T cell infiltration.

Background And Aims: Endosialin, also known as tumor endothelial marker1 or CD248, is a transmembrane glycoprotein that is mainly expressed in cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC). Our previous study has found that endosialin-positive CAFs could recruit and induce the M2 polarization of macrophages in HCC. However, whether they may regulate other types of immune cells to promoting HCC progression is not known.

YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer.

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from protumorigenic to antitumor phenotypes and to enhance ICB efficacy in prostate cancer.

Self-delivery nanodrug to manipulate tumor microenvironment for boosting photodynamic cancer immunotherapy.

Immunotherapy has captured attention for its high clinical efficacy. However, its efficacy is limited by inadequate immune activation. Therefore, a platform to activate the immune system and amplify the host's immune response against tumors is urgently needed.

Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression.

Co-delivery of Paclitaxel/Atovaquone/Quercetin to regulate energy metabolism to reverse multidrug resistance in ovarian cancer by PLGA-PEG nanoparticles.

Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment.

Amultifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed in this study, to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage , effectively alleviating RA progression in a rat adjuvant-induced arthritis model.

Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease.

Aims: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences.

Methods: Data for the study were obtained from three studies in China, Japan and the US.

A comparative study on the preparation and evaluation of solubilizing systems for silymarin.

Silymarin (SM) exhibits clinical efficacy in treating liver injuries, cirrhosis, and chronic hepatitis. However, its limited water solubility and low bioavailability hinder its therapeutic potential. The primary objective of this study was to compare the in vitro and in vivo characteristics of the four distinct SM solubilization systems, namely SM solid dispersion (SM-SD), SM phospholipid complex (SM-PC), SM sulfobutyl ether-β-cyclodextrin inclusion complex (SM-SBE-β-CDIC) and SM self-microemulsifying drug delivery system (SM-SMEDDS) to provide further insights into their potential for enhancing the solubility and bioavailability of SM.

MkcDBGAS: a reference-free approach to identify comprehensive alternative splicing events in a transcriptome.

Alternative splicing (AS) is an essential post-transcriptional mechanism that regulates many biological processes. However, identifying comprehensive types of AS events without guidance from a reference genome is still a challenge. Here, we proposed a novel method, MkcDBGAS, to identify all seven types of AS events using transcriptome alone, without a reference genome.