A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects.

Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration.

LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.

Multiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL-2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome-associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM.

Crosstalk between GBP2 and M2 macrophage promotes the ccRCC progression.

Clear cell renal cell carcinoma (ccRCC) represents a highly heterogeneous kidney malignancy associated with the poorest prognosis. The metastatic potential of advanced ccRCC tumors is notably high, posing significant clinical challenges. There is an urgent imperative to develop novel therapeutic approaches to address ccRCC metastasis.

LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is involved in biological processes critical to cancer progression, such as regulation of solute carrier transporter proteins and metabolic pathways, including mTORC1. However, the metabolic processes governed by LAPTM4B and its role in oncogenesis remain unknown.

Drying Process of HPMC-Based Hard Capsules: Visual Experiment and Mathematical Modeling.

Using plant-based polysaccharide gels to produce hard capsules is a novel application of this technology in the medicinal field, which has garnered significant attention. However, the current manufacturing technology, particularly the drying process, limits its industrialization. The work herein employed an advanced measuring technique and a modified mathematical model to get more insight into the drying process of the capsule.

Enhancing Pullulan Soft Capsules with a Mixture of Glycerol and Sorbitol Plasticizers: A Multi-Dimensional Study.

The plasticizer is crucial in the plant-based soft capsule. However, meeting the quality requirements of these capsules with a single plasticizer is challenging. To address this issue, this study first investigated the impact of a plasticizer mixture containing sorbitol and glycerol in varying mass ratios and the performance of the pullulan soft film and capsule.

miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.

Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis.

Water Treadmill Training Ameliorates Neurite Outgrowth Inhibition Associated with NGR/RhoA/ROCK by Inhibiting Astrocyte Activation following Spinal Cord Injury.

Spinal cord injury (SCI) often results in damage to or degeneration of axons. Crosstalk between astrocytes and neurons plays a pivotal role in neurite outgrowth following SCI. Rehabilitative training is a recognized method for the treatment of SCI, but the specific mechanism underlying its effect on axonal outgrowth in the central nervous system (CNS) has not yet been determined.

LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics.

Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement.

Experimental and Numerical Study on Friction and Wear Performance of Hot Extrusion Die Materials.

For the aluminium alloys produced by the hot extrusion process, the profile is shaped according to the bearing at the exit of the extrusion die. The tribological process has significant effects on the die service life, profile dimensional tolerances, and profile surface finish. Recently, new technologies have been introduced to the hot extrusion die, such as cemented carbide insert die and surface coating.

Prohibitin plays a role in the functional plasticity of macrophages.

Immunometabolism plays a crucial role in the activation and functional plasticity of immune cells, which in large determines a variety of health and disease states. Factors that integrate immunometabolism in immune cell signaling and functions are beginning to be identified. Previously, we have reported that two transgenic mouse models, Mito-Ob and mutant Mito-Ob (m-Mito-Ob), overexpressing a pleiotropic protein, prohibitin (PHB) or a mutant form of PHB (Tyr114Phe-PHB or m-PHB), respectively, developed distinct immunometabolic phenotypes.

Electroacupuncture suppresses spinal nerve ligation-induced neuropathic pain via regulation of synaptic plasticity through upregulation of basic fibroblast growth factor expression.

Background: Improving synaptic plasticity is a good way to alleviate neuropathic pain. Electroacupuncture (EA) is currently used worldwide to treat this disease, but its specific mechanisms of action need further investigation. Evidence has suggested that basic fibroblast growth factor (bFGF) plays an important role in promoting nerve regeneration and can promote the expression of vascular endothelial growth factor (VEGF).

The Predictive Role of Systemic Inflammation Response Index (SIRI) in the Prognosis of Stroke Patients.

Purpose: Stroke is a disease associated with high mortality. Many inflammatory indicators such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and red blood cell distribution width (RDW) have been documented to predict stroke prognosis, their predictive power is limited. A novel inflammatory indicator called systemic inflammatory response index (SIRI) has been advocated to have an essential role in the prognostic assessment of cancer and infectious diseases.

Ischemic stroke induces cardiac dysfunction and alters transcriptome profile in mice.

Background: Stroke can induce cardiac dysfunction in the absence of primary cardiac disease; however, the mechanisms underlying the interaction between the neurological deficits and the heart are poorly understood. The objective of this study was to investigate the effects of stroke on cardiac function and to identify the transcriptome characteristics of the heart.

Results: Stroke significantly decreased heart weight/tibia length ratio and cardiomyocyte cross-sectional areas and increased atrogin-1 and the E3 ubiquitin ligase MuRF-1, indicating myocardial atrophy in MCAO-induced mouse hearts.

[Effect of electroacupuncture on angiopoietin-1 in spinal cord of rats with neuropathic pain].

Objective: To observe the effect of electroacupuncture (EA) on the behavior, histomorphology and the expression of angiopoietin-1 (Angpt-1) in rats with spinal nerve injury, so as to explore its mechanism on neuropathic pain.

Methods: Forty-five male SD rats were randomly divided into sham, model and EA groups (=15 rats in each group). Spinal nerve ligation (SNL) of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain.

Electroacupuncture may alleviate neuropathic pain via suppressing P2X7R expression.

Neuropathic pain is a severe problem that is difficult to treat clinically. Reducing abnormal remodeling of dendritic spines/synapses and increasing the anti-inflammatory effects in the spinal cord dorsal horn are potential methods to treat this disease. Previous studies have reported that electroacupuncture (EA) could increase the pain threshold after peripheral nerve injury.

Electroacupuncture improves neuronal plasticity through the A2AR/cAMP/PKA signaling pathway in SNL rats.

Improvements in neuronal plasticity are considered to be conducive to recovery from neuropathic pain. Electroacupuncture (EA) is regarded as an effective rehabilitation method for neuropathic pain. However, the effects and potential mechanism associated with EA-induced repair of hyperesthesia are not fully understood.

Electroacupuncture effects on the P2X4R pathway in microglia regulating the excitability of neurons in the substantia gelatinosa region of rats with spinal nerve ligation.

Electroacupuncture (EA) has been used to treat neuropathic pain induced by peripheral nerve injury (PNI) by applying an electrical current to acupoints with acupuncture needles. However, the mechanisms by which EA treats pain remain indistinct. High P2X4 receptor (P2X4R) expression levels demonstrate a notable increase in hyperactive microglia in the ipsilateral spinal dorsal horn following PNI.

Water treadmill training protects the integrity of the blood-spinal cord barrier following SCI via the BDNF/TrkB-CREB signalling pathway.

Following spinal cord injury (SCI), destruction of the blood-spinal cord barrier (BSCB) leads to increased microvascular permeability and tissue oedema. The BSCB, formed by a dense network of tight junctions (TJs) and adhesion junctions (AJs) is considered a therapeutic target. Most studies have focused on the effect of drug therapy on the neurovascular system after SCI, ignoring the protection and functional recovery of the vascular system by exercise training.

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury.

Background: The permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis.

LAPTM4B controls the sphingolipid and ether lipid signature of small extracellular vesicles.

Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is a four-membrane spanning ceramide interacting protein that regulates mTORC1 signaling. Here, we show that LAPTM4B is sorted into intraluminal vesicles (ILVs) of multivesicular endosomes (MVEs) and released in small extracellular vesicles (sEVs) into conditioned cell culture medium and human urine. Efficient sorting of LAPTM4B into ILV membranes depends on its third transmembrane domain containing a sphingolipid interaction motif (SLim).

Lysosome Associated Protein Transmembrane 4B-24 Is the Predominant Protein Isoform in Human Tissues and Undergoes Rapid, Nutrient-Regulated Turnover.

Studies of lysosome associated protein transmembrane 4B (LAPTM4B) have mainly focused on the 35-kDa isoform and its association with poor prognosis in cancers. Here, by employing a novel monoclonal antibody, the authors found that the 24-kDa LAPTM4B isoform predominated in most, both healthy and malignant, human cells and tissues studied. LAPTM4B-24 lacks the extreme N-terminus and, contrary to LAPTM4B-35, failed to promote cell migration.