Enhancing the tissue penetration to improve sonodynamic immunotherapy for pancreatic ductal adenocarcinoma using membrane-camouflaged nanoplatform.

Purpose: Sonodynamic therapy (SDT) is a promising strategy as an "in situ vaccine" to enhance activation of antitumor immune responses in solid tumors. However, the dense extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) lead to hypoxia and limited penetration of most drugs, aggravating the immunosuppressive tumor microenvironment and limiting the efficacy of synergistic sonodynamic immunotherapy. Therefore, it is essential to regulate ECM in order to alleviate tumor hypoxia and enhance the efficacy of sonodynamic immunotherapy for PDAC.

Co-delivery of SN38 and MEF2D-siRNA via tLyp-1-modified liposomes reverses PD-L1 expression induced by STING activation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) exhibits an immunosuppressive tumor microenvironment, leading to a low objective response rate when immune checkpoint inhibitors (ICIs) are utilized. The cGAS-STING pathway demonstrates a powerful immune stimulatory effect, nevertheless, activation of this pathway triggers an upregulation of PD-L1, which inhibits the anti-tumor function of immune cells. The present study discovered that knockdown of MEF2D by a siRNA in H22 cells decreases the expression of PD-L1.

Characterization and therapeutic potential of MRABP9, a novel lytic bacteriophage infecting multidrug-resistant Acinetobacter baumannii clinical strains.

Acinetobacter baumannii is one of the most important pathogens of healthcare-associated infections. The rising prevalence of multidrug-resistant A. baumannii (MRAB) strains and biofilm formation impact the outcome of conventional treatment.

NIR-promoted ferrous ion regeneration enhances ferroptosis for glioblastoma treatment.

Ferroptosis, a unique iron-dependent mode of cell death characterized by lipid peroxide accumulation, holds significant potential for the treatment of glioblastoma (GBM). However, the effectiveness of ferroptosis is hindered by the limited intracellular ferrous ions (Fe) and hydrogen peroxide (HO). In this study, a novel near-infrared (NIR)-light-responsive nanoplatform (ApoE-UMSNs-GOx/SRF) based on upconversion nanoparticles (UCNPs) was developed.

NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of NF-κB Signaling and Ameliorates Mice's Depressive-like Behavior.

Microglia are believed to be the key immune effectors of the central immune microenvironment, and their dysregulation is associated with neuroinflammation and mood disorders. Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain-containing five (NLRC5) is a new member of the Nod-like receptor family. Recently, NLRC5 has been reported to be expressed by microglia.

Expression pattern of NLRC5 in the postnatal mouse brain.

Nucleotide oligomerization domain-like receptors (NLRs), belonging to a large family of pattern recognition receptors, participate in the host's first line of defense against invading pathogens. Caspase recruitment domain containing 5 (NLRC5), the largest member in the NLR family, is demonstrated to be involved in the innate immune response and inflammatory diseases far and wide. Recent studies report that NLRC5 is associated with some central nervous system (CNS) diseases.

Application of lipid nanovesicle drug delivery system in cancer immunotherapy.

Immunotherapy has gradually emerged as the most promising anticancer therapy. In addition to conventional anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy, CAR-T therapy, etc., immunotherapy can also be induced by stimulating the maturation of immune cells or inhibiting negative immune cells, regulating the tumor immune microenvironment and cancer vaccines.

Multifunctional Liposomes Enable Active Targeting and Twinfilin 1 Silencing to Reverse Paclitaxel Resistance in Brain Metastatic Breast Cancer.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for breast cancer, but PTX resistance often occurs in metastatic breast cancer. In addition, due to the poor targeting of chemotherapeutic drugs and the presence of the blood-brain barrier (BBB), it is hard to effectively treat brain metastatic breast cancer using paclitaxel. Thus, it is urgent to develop an effective drug delivery system for the treatment of brain metastatic breast cancer.

MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching.

In the immune system, Major Histocompatibility Complex class I (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where they play important roles that are significantly different from their immune functions. Classical MHC-I molecules are temporally and spatially expressed in the developing and adult CNS, where they participate in the synaptic formation, remodeling and plasticity.

Targeted NIRF/MR dual-mode imaging of breast cancer brain metastasis using BRBP1-functionalized ultra-small iron oxide nanoparticles.

Tumor metastasis to brain is the main clinical manifestation of patients with advanced breast cancer, leading to poor survival prognosis. In order to detect the early incidence of brain metastasis, it is urgent to develop hypersensitive contrast agents for multimode imaging. In this study, PEG-phospholipids coated, a phage play derived peptide, BRBP1 peptide modified ultra-small iron oxide nanoparticles were prepared for targeted NIRF and MR imaging of breast cancer brain metastasis.

Neuronal NLRC5 regulates MHC class I expression in Neuro-2a cells and also during hippocampal development.

Major histocompatibility Complex class I (MHC I) molecules are ubiquitously expressed, being found in most nucleated cells, where they are central mediators of both the adaptive and innate immune responses. Recent studies have shown that MHC I are also expressed in the developing brain where they participate in synapse elimination and plasticity. Up-regulation of MHC I within the developing brain has been reported, however, the mechanism(s) regulating this developmental up-regulation of neuronal MHC I remains unknown.

MHC Class I Molecules and PirB Shape Neuronal Morphology by Affecting the Dendritic Arborization of Cortical Neurons.

Neuronal MHC class I proteins have been previously reported to regulate synaptic plasticity. Several reports indicate MHC class I proteins are expressed early during development of the nervous system, suggesting they may also play a role in neuronal development. Using cultured cortical neurons, we show MHC class I proteins aggregate at specific sites in neuronal cell bodies, which overlap with the actin cytoskeleton.

Modulation of the gamma-secretase activity as a therapy against human hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. The discovery of new therapies against HCC is highly dependable on finding molecules which play essential roles in cancer development. The objective of this study was to evaluate the activity of gamma secretase (γ-secretase), and the antitumor effects of a γ-secretase inhibitor (GSI) in HCC.

Non-Invasive Monitoring of CNS MHC-I Molecules in Ischemic Stroke Mice.

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. The expression of major histocompatibility complex class I (MHC-I) molecules in the central nervous system, which are silenced under normal physiological conditions, have been reported to be induced by injury stimulation. The purpose of this study was to determine whether MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke and to assess whether a high-affinity peptide specific for MHC-I molecules could be applied in the near-infrared imaging of cerebral ischemic mice.

Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. The main features of AD are the pathological changes of density and distribution of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. The processing of amyloid beta precursor protein (APP) to β-amyloid peptide (Aβ) is one of the critical events in the pathogenesis of AD.

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice.

Purpose: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice.

Methods: CD90(+) LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics.

Production and application of polyclonal and monoclonal antibodies against Spiroplasma eriocheiris.

A new species of spiroplasma, Spiroplasma eriocheiris (S. eriocheiris), was identified as a lethal pathogen of tremor disease (TD) in Chinese mitten crab recently. In order to acquire appropriate biological and diagnostic tools for characterizing this newly discovered pathogen, 5 monoclonal antibodies (mAbs) and a polyclonal antibody (pAb) against S.

Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

MHC class I (MHC-I) molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s) underlying activity-dependent MHC-I expression using hippocampal neurons.

Developmental expression and localization of MHC class I molecules in the human central nervous system.

Recent animal studies have found neuronal expression of major histocompatibility complex (MHC) class I in the central nervous system (CNS). However, the developmental expression profiles of MHC class I in human CNS remain unclear. Here, we systemically evaluate the expression and subcellular localization of MHC class I molecules during human CNS development using immunohistochemistry and immunofluorescence.

Spatial-Temporal Expression of Non-classical MHC Class I Molecules in the C57 Mouse Brain.

Recent studies clearly demonstrate major histocompatibility complex (MHC) class I expression in the brain plays an important functional role in neural development and plasticity. A previous study from our laboratory demonstrated the temporal and spatial expression patterns of classical MHC class I molecules in the brain of C57 mice. Studies regarding non-classical MHC class I molecules remain limited.

Enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA on human brain metastatic breast cancer.

Novel molecularly targeted agents that block the development and metastasis of human brain metastatic breast cancer hold great promise for their translational value. In this study, we constructed a novel targeting composite peptide BRBP1-TAT-KLA comprising of three elements: a brain metastatic breast carcinoma cell (231-BR)-binding peptide BRBP1, a cell penetrating peptide TAT, and a proapoptotic peptide KLA. This composite peptide efficiently internalized in 231-BR cells and consequently induced mitochondrial damage and cellular apoptosis.

Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo.

Background: This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored.

20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro.

20(s)-ginsenoside Rg3 is extracted from traditional Chinese medicine, red ginseng. However, due to its poor aqueous solubility and low oral bioavailability, the use of 20(s)-Rg3 is limited. This study aimed to explore a method of preparing nano-sized 20(s)-ginsenoside Rg3 particle named 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres (20(s)-Rg3/HSAMNP) to change dosage form to improve its aqueous solubility and bioavailability.

Identification and characterization of a novel phage display-derived peptide with affinity for human brain metastatic breast cancer.

A novel peptide, BRBP1 (MYPWTEPSYLSN), was identified using an in vitro phage biopanning strategy against human brain-seeking breast carcinoma cells (231-BR cells).The peptide-phage clone, BRBP1-M13 displaying BRBP1 sequence, specifically bound to 231-BR cells and the binding could be competitively abolished by BRBP1. In vivo distribution studies showed that BRBP1-M13 preferentially homed to the 231-BR tumors.

Interaction of parental KIR and fetal HLA-C genotypes with the risk of preeclampsia.

Objective: The aim of this study is to investigate whether certain combination of maternal killer cell immunoglobulin-like receptors (KIR) and fetal human leukocyte antigen-C (HLA-C) is risk for preeclampsia in the Chinese Han population.

Methods: A case-control study was conducted in 47 pregnant women with preeclampsia and 54 normal pregnant women. Twelve KIR genes were genotyped by PCR-sequence-specific primer in mothers.