A Novel Cell-Penetrating Peptide-Vascular Endothelial Growth Factor Small Interfering Ribonucleic Acid Complex That Mediates the Inhibition of Angiogenesis by Human Umbilical Vein Endothelial Cells and in an Ex Vivo Mouse Aorta Ring Model.

Angiogenesis is mediated by vascular endothelial growth factor (VEGF), a protein that plays a key role in wound healing, inflammatory diseases, cardiovascular processes, ocular diseases, and tumor growth. Indeed, modulation of angiogenesis represents a potential approach to treating cancer and, as such, therapeutic approaches targeting VEGF and its receptors have been widely investigated as part of the broader search for curative interventions. Equally, RNA interference is a powerful tool for treating diseases, but its application as a disease treatment has been limited in part because of a lack of efficient small interfering RNA (siRNA) delivery systems.

Production of a monoclonal antibody targeting the SARS-CoV-2 Omicron spike protein and analysis of SARS-CoV-2 Omicron mutations related to monoclonal antibody resistance.

SARS-CoV-2 mutations have resulted in the emergence of multiple concerning variants, with Omicron being the dominant strain presently. Therefore, we developed a monoclonal antibody (mAb) against the spike (S) protein of SARS-CoV-2 Omicron for therapeutic applications. We established the 1E3H12 mAb, recognizing the receptor binding domain (RBD) of the Omicron S protein, and found that the 1E3H12 mAb can efficiently recognize the Omicron S protein with weak affinity to the Alpha, Beta, and Mu variants, but not to the parental strain and Delta variant.

Tailored biosynthesis of diosmin through reconstitution of the flavonoid pathway in .

The flavonoid diosmin (diosmetin 7--rutinoside) is used as a therapeutic agent for disorders of the blood vessels such as hemorrhoids and varicose veins. Diosmin is commercially produced using semi-synthetic methods involving the oxidation of hesperidin, the most abundant flavonoid in citrus fruits. However, this method produces byproducts that are toxic to the environment, and new sustainable methods to produce diosmin are required.

Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic .

Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 samples (and the closely related outgroup species, from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres.

N121T and N121S substitutions on the SARS-CoV-2 spike protein impact on serum neutralization.

The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment.

Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model.

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M were revealed to significantly reduce viral susceptibility to nirmatrelvir , there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors.

Cellular metabolism of substance P produces neurokinin-1 receptor peptide agonists with diminished cyclic AMP signaling.

Substance P (SP) is released from sensory nerves in the arteries and heart. It activates neurokinin-1 receptors (NK1Rs) causing vasodilation, immune modulation, and adverse cardiac remodeling. The hypothesis was tested: SP and SP metabolites activate different second messenger signaling pathways.

Target-based discovery of a broad-spectrum flukicide.

Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases-for example, the parasitic blood fluke infection schistosomiasis-are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola because of a single amino acid change within the target of PZQ, a transient receptor potential ion channel in the melastatin family (TRPM), in Fasciola species.

Analysis of SARS-CoV-2 omicron mutations that emerged during long-term replication in a lung cancer xenograft mouse model.

SARS-CoV-2 Omicron has the largest number of mutations among all the known SARS-CoV-2 variants. The presence of these mutations might explain why Omicron is more infectious and vaccines have lower efficacy to Omicron than other variants, despite lower virulence of Omicron. We recently established a long-term in vivo replication model by infecting Calu-3 xenograft tumors in immunodeficient mice with parental SARS-CoV-2 and found that various mutations occurred majorly in the spike protein during extended replication.

Butein Increases Resistance to Oxidative Stress and Lifespan with Positive Effects on the Risk of Age-Related Diseases in .

Butein is a flavonoid found in many plants, including dahlia, butea, and coreopsis, and has both antioxidant and sirtuin-activating activities. In light of the postulated role of free radicals in aging, we examined the effects of butein on aging and on genetic or nutritional models of age-related diseases in . Butein showed radical scavenging activity and increased resistance to oxidative stress in .

A mouse xenograft long-term replication yields a SARS-CoV-2 Delta mutant with increased lethality.

We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein.

Contribution of HSP90 Cleavage to the Cytotoxic Effect of Suberoylanilide Hydroxamic Acid and the Involvement of TXNIP in HSP90 Cleavage.

Heat shock protein (HSP) 90 is expressed in most living organisms, and several client proteins of HSP90 are necessary for cancer cell survival and growth. Previously, we found that HSP90 was cleaved by histone deacetylase (HDAC) inhibitors and proteasome inhibitors, and the cleavage of HSP90 contributes to their cytotoxicity in K562 leukemia cells. In this study, we first established mouse xenograft models with K562 cells expressing the wild-type or cleavage-resistant mutant HSP90β and found that the suppression of tumor growth by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was interrupted by the mutation inhibiting the HSP90 cleavage .

-Mediated Transformation of the Aquatic Fungus FBCC-F1546.

is a useful fungus known for its ability to mineralise lignin during primary metabolism and decompose polycyclic aromatic hydrocarbons (PAHs). However, no functional genetic analysis techniques have been developed yet for this fungus, specifically in terms of transformation. In this study, we applied an -mediated transformation (ATMT) system to for a functional gene analysis.

Gene editing of authentic generates dihydroflavonol-accumulating Chinese cabbage.

Flavonols are the major class of flavonoids of green Chinese cabbage ( subsp. ). The genome harbors seven genes (s), but they have not been functionally characterized.

The anthelmintic meclonazepam activates a schistosome transient receptor potential channel.

Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago.

Analysis of spike protein variants evolved in a novel long-term replication model for SARS-CoV-2.

Introduction: The spectrum of SARS-CoV-2 mutations have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants. Calu-3 human lung cancer cells persistently grow without apoptosis and release low virus titers after infection.

The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPM Orthologs.

The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPM, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes.

SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line.

Target-based discovery of a broad spectrum flukicide.

Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus .

Isolation of with Enhanced Nitric Oxide Synthesis from Korean Traditional Fermented Food and Investigation of Its Probiotic Properties.

Nitric oxide (NO) is a free radical associated with physiological functions such as blood pressure regulation, cardiovascular health, mitochondrial production, calcium transport, oxidative stress, and skeletal muscle repair. This study aimed to isolate strains with enhanced NO production from the traditional Korean fermented food, jangajji, and evaluate their probiotic properties for industrial purposes. When cells were co-cultured with various bacterial stimulants, NO production generally increased, and NO synthesis was observed in the range of 20-40 mg/mL.

Probiotic Properties of JBCC 106 and Its Lactic Acid Fermentation on Broccoli Juice.

To understand the biological roles of strains as probiotics isolated from the traditional Korean fermented food, , was selected based on its high cinnamoyl esterase (CE) and antioxidant activities. The acid and bile stability, intestinal adhesion, antagonistic activity against human pathogens, cholesterol-lowering effects, and immune system stimulation without inflammatory effects were evaluated. Nitric oxide (NO) levels were measured in co-culture with various bacterial stimulants.

Sniffer worm, C. elegans, as a toxicity evaluation model organism with sensing and locomotion abilities.

Additive manufacturing, or 3D printing, has revolutionized the way we create objects. However, its layer-by-layer process may lead to an increased incidence of local defects compared to traditional casting-based methods. Factors such as light intensity, depth of light penetration, component inhomogeneity, and fluctuations in nozzle temperature all contribute to defect formations.

PROTEIN PHOSPHATASE 2C08, a Negative Regulator of Abscisic Acid Signaling, Promotes Internode Elongation in Rice.

Clade A protein phosphatase 2Cs (PP2CAs) negatively regulate abscisic acid (ABA) signaling. Here, we investigated the functions of OsPP2CAs and their crosstalk with ABA and gibberellic acid (GA) signaling pathways in rice (). Among the nine OsPP2CAs, OsPP2C08 had the highest amino acid sequence similarity with OsPP2C51, which positively regulates GA signaling in rice seed germination.