Cu-Labeled Boronic-Acid-Conjugated Porphyrin: A Novel Agent for PET Imaging and Boron Neutron Capture Therapy.

Radiometal-labeled porphyrin derivatives have emerged candidates for targeted brain tumor imaging and therapy. In this study, we synthesized a boronic-acid-conjugated porphyrin and radiolabeled it with Cu to evaluate its dual-function potential for PET imaging and boron neutron capture therapy (BNCT). The Cu-labeled 5,10,15,20-(tetra-4-dihydroxyborylphenyl)-porphyrin ([Cu]-Cu-TDBP) exhibited excellent serum stability and significant uptake in U87MG cells.

JAK-STAT inhibitory effect of IN-115314, a novel small molecule inhibitor, and pharmacokinetic/pharmacodynamic study in canine.

Background And Purpose: The JAK-STAT signalling pathway has been extensively spotlighted as a therapeutic target for various diseases. This study assessed the inhibitory effects of a novel small molecule, IN-115314, on JAK-STAT pathway.

Experimental Approach: The IC values of IN-115314 for JAK1-pSTAT3 and JAK2-pSTAT5 were determined in canine whole blood cells and TF-1 cells.

Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model.

The increasing use of SARS-CoV-2 mRNA vaccines has raised concerns about their potential toxicological effects, necessitating further investigation to ensure their safety. To address this issue, we aimed to evaluate the toxicological effects of SARS-CoV-2 mRNA vaccine candidates formulated with four different types of lipid nanoparticles in ICR mice, focusing on repeated doses and administration routes. We conducted an extensive analysis in which mice received the mRNA vaccine candidates intramuscularly (50 μg/head) twice at 2-week intervals, followed by necropsy at 2 and 14 dpsi (days post-secondary injection).

Nrf2-Dependent Adaptation to Oxidative Stress Protects Against Progression of Diabetic Nephropathy.

Adaptation to oxidative stress is essential for maintaining protein and redox homeostasis in mammalian cells. Palmitic acid (PA) plays a central role in oxidative stress and immunoproteasome regulation in podocytes and diabetes, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial impact on diabetes. The role of Nrf2 in adaptation to oxidative stress and regulation of immunoproteasome by PA and EPA/DHA in podocytes and diabetic kidneys is not well defined.

Preclinical evaluation of [F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson's disease: pharmacokinetic and efficacy analysis.

Background: N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). I- and F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [F]FP-CIT as a potential diagnostic biomarker are scarce.

Impact of IL-1β on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1β maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1β in the host's defense against MAB.

Water Extract of Desalted Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice.

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice.

Porphyrin-Based Brain Tumor-Targeting Agents: [Cu]Cu-porphyrin and [Cu]Cu-TDAP.

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-,-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four ,-dimethyl-4--phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin.

Comparison of the Effects of DOTA and NOTA Chelators on Cu-Cudotadipep and Cu-Cunotadipep for Prostate Cancer.

Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, Cu-cudotadipep and Cu-cunotadipep, on pharmacokinetics.

Methods: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota.

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation.

Feasibility of Gd-Based prostate cancer targeted magnetic resonance agents using prostate specific membrane antigen.

The aim of this work was to evaluate Gd-FC705, a prostate-specific membrane antigen (PSMA)-targeted MRI contrast agent. The r and r relaxivities of Gd-FC705 are 5.94 mMs and 17.

The sesquiterpene lactone estafiatin exerts anti-inflammatory effects on macrophages and protects mice from sepsis induced by LPS and cecal ligation puncture.

Background: Previously, we found that the water extract of Artermisia scoparia Waldst. & Kit suppressed the cytokine production of lipopolysaccharide (LPS)-stimulated macrophages and alleviated carrageenan-induced acute inflammation in mice. Artemisia contains various sesquiterpene lactones and most of them exert immunomodulatory activity.

Type I Interferons Are Involved in the Intracellular Growth Control of by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.

(MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages.

Porphyrin-Based Tumor-Targeting Theranostic Agent: Gd-TDAP.

The aim of this work was to evaluate a tumor-targeting porphyrin-based gadolinium complex (Gd-TDAP) for use as an MR/optical imaging agent and potential therapeutic agent. Gd-TDAP had higher longitudinal relaxivity (11.8 mM s) than a commercial MRI contrast agent (Omniscan; 3.

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses.

Unlabelled: Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. β-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and β-glucan on macrophage-mediated immune responses.

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.

Problem: Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence of APOs.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

Background: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood.

Objective: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR).

Water extract of Artemisia scoparia Waldst. & Kitam suppresses LPS-induced cytokine production and NLRP3 inflammasome activation in macrophages and alleviates carrageenan-induced acute inflammation in mice.

Ethnopharmacological Relevance: Artemisia scoparia Waldst. & Kitam (A. scoparia) is a perennial herbal plant that is widely used as a folk remedy in Asian countries.

Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection with in Mice.

is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects.

IL-10 Protects Mice From the Lung Infection of and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages.

Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after infection, compared to WT mice.

Expression of Transcripts in Marmoset Oocytes Retrieved during Follicle Isolation Without Gonadotropin Induction.

The in vitro maturation of oocytes is frequently used as an assisted reproductive technique (ART), and has been successfully established in humans and rodents. To overcome the limitations of ART, novel procedures for the in vitro maturation of early follicles are emerging. During the follicle isolation procedure, the unintended rupture of each follicle leads to a release of extra oocytes.

Nucleotide-binding oligomerization domain 1 is dispensable for host immune responses against pulmonary infection of in mice.

Nucleotide-binding domain 1 (Nod1) is a cytosolic receptor that is responsible for the recognition of a bacterial peptidoglycan motif containing -diaminophimelic acid. In this study, we sought to identify the role of Nod1 in host defense against pulmonary infection by multidrug resistant . Wildtype (WT) and Nod1-deficient mice were intranasally infected with 3×10 CFU of and sacrificed at 1 and 3 days post-infection (dpi).