Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.

Adeno-associated virus (AAV) is characterized by non-pathogenicity, long-term infection, and broad tropism and is actively developed as a vector virus for gene therapy products. AAV is classified into more than 100 serotypes based on differences in the amino acid sequence of the capsid protein. Endocytosis involves the uptake of viral particles by AAV and accessory receptors during AAV infection.

Current Strategies and Therapeutic Applications of Mesenchymal Stem Cell-Based Drug Delivery.

Mesenchymal stem cells (MSCs) have emerged as a promising approach for drug delivery strategies because of their unique properties. These strategies include stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, immunomodulatory effects, stem cell-laden scaffolds, and scaffold-free stem cell sheets. MSCs offer advantages such as low immunogenicity, homing ability, and tumor tropism, making them ideal for targeted drug delivery systems.

Immunological Regulation of Gut-Tropic Immune Cells by Extracellular Vesicles.

The remarkable diversity of lymphocytes, essential components of the immune system, serves as an ingenious mechanism for maximizing the efficient utilization of limited host defense resources. While cell adhesion molecules, notably in gut-tropic T cells, play a central role in this mechanism, the counterbalancing molecular details have remained elusive. Conversely, we've uncovered the molecular pathways enabling extracellular vesicles secreted by lymphocytes to reach the gut's mucosal tissues, facilitating immunological regulation.

Hyposecretion of cervical MUC5B is related to preterm birth in pregnant women after cervical excisional surgery.

Problem: Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy.

Adenoid cystic carcinoma of the orbit without lacrimal gland involvement and with intracranial extension: A case report.

We present a 76-year-old female with a 6-year history of decreased vision in the right eye and right-sided facial neuralgia. She had a T1 isointense and T2 isointense enhancing lesion in the right orbit and the middle cranial fossa on MRI examination. Granulomatous disease or meningioma was suspected, however, after removal, the tumor was identified by pathology as adenoid cystic carcinoma (ACC).

Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating.

[Hierarchical Decision-Making Mechanism of the Frontal Lobe].

Actions performed by humans require various levels of volitional control, ranging from highly practiced, automatic actions to those done in unfamiliar environments which necessitate deliberate controls. The multiple cortical motor areas in the frontal lobe regulate actions that vary in the levels of automaticity vs. intentionality.

Development, Safety, Issues, and Challenges of the SARS-CoV-2 Vaccine.

It has been reported that some mutant strains of the new coronavirus escape from neutralizing antibodies acquired by recoverees and vaccine recipients, in which the Omicron strain (B [...

Extracellular Vesicle-Based SARS-CoV-2 Vaccine.

Messenger ribonucleic acid (RNA) vaccines are mainly used as SARS-CoV-2 vaccines. Despite several issues concerning storage, stability, effective period, and side effects, viral vector vaccines are widely used for the prevention and treatment of various diseases. Recently, viral vector-encapsulated extracellular vesicles (EVs) have been suggested as useful tools, owing to their safety and ability to escape from neutral antibodies.

Ensemble Learning, Deep Learning-Based and Molecular Descriptor-Based Quantitative Structure-Activity Relationships.

A deep learning-based quantitative structure-activity relationship analysis, namely the molecular image-based DeepSNAP-deep learning method, can successfully and automatically capture the spatial and temporal features in an image generated from a three-dimensional (3D) structure of a chemical compound. It allows building high-performance prediction models without extracting and selecting features because of its powerful feature discrimination capability. Deep learning (DL) is based on a neural network with multiple intermediate layers that makes it possible to solve highly complex problems and improve the prediction accuracy by increasing the number of hidden layers.

Non-overlapping sets of neurons encode behavioral response determinants across different tasks in the posterior medial prefrontal cortex.

Higher mammals are able to simultaneously learn and perform a wide array of complex behaviors, which raises questions about how the neural representations of multiple tasks coexist within the same neural network. Do neurons play invariant roles across different tasks? Alternatively, do the same neurons play different roles in different tasks? To address these questions, we examined neuronal activity in the posterior medial prefrontal cortex of primates while they were performing two versions of arm-reaching tasks that required the selection of multiple behavioral tactics (i.e.

Advances in Purification, Modification, and Application of Extracellular Vesicles for Novel Clinical Treatments.

Extracellular vesicles (EV) are membrane vesicles surrounded by a lipid bilayer membrane and include microvesicles, apoptotic bodies, exosomes, and exomeres. Exosome-encapsulated microRNAs (miRNAs) released from cancer cells are involved in the proliferation and metastasis of tumor cells via angiogenesis. On the other hand, mesenchymal stem cell (MSC) therapy, which is being employed in regenerative medicine owing to the ability of MSCs to differentiate into various cells, is due to humoral factors, including messenger RNA (mRNA), miRNAs, proteins, and lipids, which are encapsulated in exosomes derived from transplanted cells.

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery.

Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression.

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation.

Extracellular vesicles (EVs) produced by various immune cells, including B and T cells, macrophages, dendritic cells (DCs), natural killer (NK) cells, and mast cells, mediate intercellular communication and have attracted much attention owing to the novel delivery system of molecules in vivo. DCs are among the most active exosome-secreting cells of the immune system. EVs produced by cancer cells contain cancer antigens; therefore, the development of vaccine therapy that does not require the identification of cancer antigens using cancer-cell-derived EVs may have significant clinical implications.

Cervical MUC5B and MUC5AC are Barriers to Ascending Pathogens During Pregnancy.

Context: Cervical excision is a risk factor for preterm birth. This suggests that the cervix plays an essential role in the maintenance of pregnancy.

Objective: We investigated the role of the cervix through proteomic analysis of cervicovaginal fluid (CVF) from pregnant women after trachelectomy surgery, the natural model of a lack of cervix.

Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition.

The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo.

Subjective achievement from psychiatry rotation in the Japanese postgraduate residency system: a longitudinal questionnaire study.

Background: Psychiatry rotation has been mandatory in the Japanese postgraduate residency system since 2020. Some psychiatry-related competency items are stipulated as mandatory for residents. The current study aimed to clarify whether psychiatry rotation affected residents' subjective achievement of these competency items.

Combination therapy of modified electroconvulsive therapy and long-acting injectable aripiprazole for dopamine supersensitivity psychosis: a case report.

In the treatment of schizophrenia, long-term pharmacotherapy with D2-receptor antagonists can induce dopamine supersensitivity psychosis (DSP). We report a male patient with schizophrenia with suspected DSP due to excessive polypharmacy. He was hospitalized for several years.

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine.

Extracellular vesicles (EVs) are lipid bilayer membrane particles that play critical roles in intracellular communication through EV-encapsulated informative content, including proteins, lipids, and nucleic acids. Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal ability derived from bone marrow, fat, umbilical cord, menstruation blood, pulp, etc., which they use to induce tissue regeneration by their direct recruitment into injured tissues, including the heart, liver, lung, kidney, etc.

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications.

Since it has been reported that extracellular vesicles (EVs) carry cargo using cell-to-cell comminication according to various in vivo situations, they are exprected to be applied as new drug-delivery systems (DDSs). In addition, non-coding RNAs, such as microRNAs (miRNAs), have attracted much attention as potential biomarkers in the encapsulated extracellular-vesicle (EV) form. EVs are bilayer-based lipids with heterogeneous populations of varying sizes and compositions.

Immune Modulation Using Extracellular Vesicles Encapsulated with MicroRNAs as Novel Drug Delivery Systems.

Self-tolerance involves protection from self-reactive B and T cells via negative selection during differentiation, programmed cell death, and inhibition of regulatory T cells. The breakdown of immune tolerance triggers various autoimmune diseases, owing to a lack of distinction between self-antigens and non-self-antigens. Exosomes are non-particles that are approximately 50-130 nm in diameter.