TRPtracker: a community database for monitoring praziquantel sensitivity at TRPM variants.

The anthelmintic praziquantel (PZQ) has been used for decades as the clinical therapy for schistosomiasis, and remains the only available drug. As a cheap and effective drug therapy for all human disease-causing species, usage of PZQ underpins mass drug administration strategies aimed at eliminating schistosomiasis as a public health problem by 2030. Concern over the potential emergence of resistance to PZQ is therefore warranted, as it would constitute a major threat to this approach.

Xanthoxyline prevents aging and neuronal damage by activating autophagy and DAF-16 expression in .

Xanthoxyline, a plant-derived phytochemical, has anti-bacterial, anti-fungal, and anti-cancer activities. We intended to investigate the effect of xanthoxyline on the response to oxidative stress, aging, and Parkinson's disease. The effects of dietary supplementation with xanthoxyline on stress response and aging were examined using as a model system.

Target-Based Design of Praziquantel Analogs at Cestode TRPM.

The drug praziquantel (PZQ) has been used for decades to treat clinical and veterinary infections caused by parasitic flatworms. Although PZQ is efficacious against many different types of flukes and tapeworms, PZQ activity is lower against certain types of parasites, including pseudophyllidean cestodes. The target of PZQ is a parasitic flatworm transient receptor potential ion channel (TRPM), and interrogation of this target affords the opportunity to understand why PZQ efficacy varies between different parasites and how target-based design strategies could help deliver new analogs with improved efficacy against currently hard-to-treat diseases.

Synthetic homoisoflavane derivatives suppress the growth of colorectal cancer cells by disturbing microtubule dynamics.

Microtubules, composed of tubulin proteins, have a crucial role in various cellular processes, including cell cycle regulation. The dynamic instability of microtubules has been an attractive target for cancer therapy. This study investigated two potent anticancer drug candidates, homoisoflavane derivatives SH-19021 and SHA-035, and evaluated their potential as microtubule-targeting agents (MTAs) in human colorectal cancer cells.

Therapeutic Intervention of an Intranasally Administered Monoclonal Antibody Targeting the SARS-CoV-2 Omicron Spike Protein Against SARS-CoV-2 Omicron Infection in Mice.

SARS-CoV-2 has evolved into several variants of concern, with Omicron and its subvariants currently being the most prevalent. Previously, we developed a mouse monoclonal antibody (m1E3H12 mAb) specific to the receptor binding domain of SARS-CoV-2 Omicron spike protein, and the mAb showed neutralizing activity against SARS-CoV-2 Omicron BA.1 and its subvariants BA.

Inhibition of serotonin-Htr2b signaling in skeletal muscle mitigates obesity-induced insulin resistance.

Obesity-induced insulin resistance is a major cause of metabolic disorders, including type 2 diabetes mellitus. Although peripheral serotonin (5-hydroxytryptamine, 5-HT) has been implicated in energy balance and metabolism, its effect on skeletal muscle insulin sensitivity remains unclear. Here we identified the 5-HT receptor 2b (Htr2b) as a critical regulator of insulin sensitivity and energy metabolism in the skeletal muscle.

Biochemical evaluation of molecular parts for flavonoid production using plant synthetic biology.

Among organisms on Earth, plants have the unique ability to produce a wide variety of biomolecules using soil nutrients, air, and solar energy. Therefore, plants are regarded as the most productive and cost-efficient bioreactors among living organisms. Flavonoids, a major group of secondary metabolites exclusively produced in plants, play crucial roles in plant physiology and have various effects on human health.

Report of 10 Unrecorded Fungi from Freshwater Environment in Korea.

Research on fungi isolated from freshwater environments contribute to expanding the fungal diversity and species inventory of freshwater ecosystems, as well as aiding in understanding the roles they play within these ecosystems. This study presents detailed descriptions and phylogenetic tree of 10 fungal species isolated from various freshwater environments in South Korea. These species were isolated from freshwater environments, such as plantlitter, sediment, and filtered freshwater.

The Immune-Enhancing Effects of a L-30 Extract Through the NF-κB and MAPK Pathways in RAW264.7.

Immune enhancement is an important factor that not only helps prevent infections but also affects overall health. This study aims to evaluate the immunostimulatory effects of a novel strain, L-30, and to elucidate its underlying mechanisms. The extract obtained from L-30 significantly increased phagocytosis and the production of NO and ROS in RAW264.

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.