Therapeutic effect of aged garlic extract on gingivitis in dogs.

Periodontal disease is one of the most common dental health problems in dogs. Clinical studies in humans have shown that aged garlic extract (AGE), which contains stable and water-soluble sulfur-containing bioactive compounds, improves the symptoms of periodontal diseases. Our previous study demonstrated that oral administration of AGE in healthy Beagle dogs at 90 mg/kg/day for 12 weeks had no adverse effects such as hemolytic anemia, which is well known to occur as a result of ingestion of species, including onions and garlic, in dogs.

Clinical and Pathological Findings in Fatal Cases of Severe Fever With Thrombocytopenia Syndrome With High Viremia in Cats.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the SFTS virus (SFTSV). SFTSV causes severe symptoms both in humans and cats. In this study, we report the clinical and pathological findings of 4 fatal cases of cats with high SFTS viremia levels.

Decomposition of multifunctionalized α-alkoxyalkyl-hydroperoxides derived from the reactions of Criegee intermediates with diols in liquid phases.

The oxidation of volatile organic compounds in the atmosphere produces organic hydroperoxides (ROOHs) that typically possess not only -OOH but also other functionalities such as -OH and -C(O). Because of their high hydrophilicity and low volatility, such multifunctionalized ROOHs are expected to be taken up in atmospheric condensed phases such as aerosols and fog/cloud droplets. However, the characteristics of ROOHs that control their fates and lifetimes in liquid phases are poorly understood.

Challenging Approach to the Development of Novel Estrogen Receptor Modulators Based on the Chemical Properties of Guaiazulene.

Tamoxifen, a therapeutic agent for breast cancer, has been associated with genetic polymorphisms in the metabolism of ,-dialkylaminoethyl substituent, which plays an important role in the expression of selective estrogen receptor modulator (SERM) activity. To solve this problem, we developed a novel estrogen receptor (ER) modulator, Az-01, on the basis of the aromaticity, dipole moment, and isopropyl group of guaiazulene. Az-01 showed four-fold lower binding affinity for ER than E2 but had similar ER-binding affinity to that of 4-hydroxytamoxifen (4-HOtam).

Development of Force Field Parameters for p-Carborane to Investigate the Structural Influence of Carborane Derivatives on Drug Targets by Complex Formation.

Androgen receptor (AR) has a key role in the development and progression of prostate cancer, and AR antagonists are used for its remedy. Recently, carborane derivatives, which are carbon-containing boron clusters have attracted attention as new AR ligands. Here we determined the force field parameters of 10-vertex and 12-vertex p-carborane to facilitate in silico drug design of boron clusters.

Antidepressant effect of BE360, a new selective estrogen receptor modulator, activated via CREB/BDNF, Bcl-2 signaling pathways in ovariectomized mice.

We have previously reported that the carborane compound BE360, a novel selective estrogen receptor modulator, has a therapeutic potential against dementia. This study aimed to explore the effects and underlying mechanisms of BE360 on depression-like behaviors in ovariectomized (OVX) mice subjected to subchronic stress, which are postmenopausal depression models. BE360 was subcutaneously administrated using a mini-osmotic pump, for 2 weeks.

Systemic Inonotus sp. Infection in a dog.

A 3-years-old male golden retriever was presented for decreased activity (lethargy), anorexia, and titubation. Superficial lymph nodes were enlarged, and arrhythmia and tachycardia were auscultated. Fungal hyphae-like structures were detected in the biopsy samples from an enlarged lymph node and spleen.

Design and Synthesis of Novel Breast Cancer Therapeutic Drug Candidates Based upon the Hydrophobic Feedback Approach of Antiestrogens.

Based upon hydrophobic feedback approaches, we designed and synthesized novel sulfur-containing ERα modulators ( and ) as breast cancer therapeutic drug candidates. The tetrahydrothiepine derivative showed the highest binding affinity toward ERα because of its high hydrophobicity, and it acted as an agonist toward MCF-7 cell proliferation. The corresponding alkylamino derivative maintained high binding affinity to ERα and potently inhibited MCF-7 cell proliferation (IC: 0.

ER subtype selectivity of m-carborane-containing phenols: C-alkyl groups on the m-carborane cage enhance ERα selectivity.

Estrogen receptor (ER) exhibits two subtypes, ERα and ERβ, whose biological functions are quite different despite expression in the same tissues. We developed diiodo-m-carborane derivative 3a, which showed 14-fold selectivity for ERβ with high binding affinity toward ERβ. Interestingly, introduction of an alkyl group into the carbon atom of the m-carborane cage of 3a markedly enhanced the binding affinity toward ERα and decreased affinity toward ERβ.

An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes.

Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer's disease, Parkinson's disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes.

Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition.

m-Carborane-containing compound 1a was identified as a cell growth inhibitor from a random screening of a boron compound library. As 1a is a mixture of diastereomers due to the presence of two chiral carbons, we designed achiral derivatives 2-4 and studied the structure-activity relationships of the methoxy groups on the benzene ring. 3,4,5-Trimethoxybenzyl derivative 2a and 3,4,5-trimethoxybenzoyl derivative 3a showed more potent anti-cancer activity against the human breast cancer cell line MDA-MB-453 than lead compound 1a.

Benzolactam-related compounds promote apoptosis of HIV-infected human cells via protein kinase C-induced HIV latency reversal.

Latency-reversing agents (LRAs) are considered a potential strategy for curing cells of HIV-1 infection. Certain protein kinase C (PKC) activators have been previously reported to be LRAs because they can reverse HIV latency. In the present study, we examined the activities of a panel of benzolactam derivatives against cells latently infected with HIV.

Identification of Gammaherpesvirus 1 in Tsushima Leopard Cats () on Tsushima Island, Japan.

gammaherpesvirus 1 (FcaGHV1) is a widely endemic infection of domestic cats. Current epidemiological data identify domestic cats as the sole natural host for FcaGHV1. The Tsushima leopard cat (TLC; is a critically endangered species that lives only on Tsushima Island, Nagasaki, Japan.

Novel androgen receptor full antagonists: Design, synthesis, and a docking study of glycerol and aminoglycerol derivatives that contain p-carborane cages.

Based on the co-crystal structure of bicalutamide with a T877A-mutated androgen receptor (AR), glycerol and aminoglycerol derivatives were designed and synthesized as a novel type of carborane-containing AR modulators. The (R)-isomer of 6c, whose chirality is derived from the glycerol group, showed 20 times more potent cell inhibitory activity against LNCaP cell lines expressing T877A-mutated AR than the corresponding (S)-isomer. Docking studies of both isomers with AR suggested that (R)-6c is in closer spatial proximity to helix-12 of the AR than (S)-6c, which is the most important common motif in the secondary structure of AR for the expression of antagonistic activity.

Design and synthesis of p-carborane-containing sulfamates as multitarget anti-breast cancer agents.

The development of multitarget anticancer agents is of high interest to medicinal chemists in terms of overcoming drug resistance and preventing cancer-cell migration. Based on the structure of the potent carborane-containing estrogen BE120, non-steroidal multitarget anti-breast cancer agent candidates 1a-1j were designed and synthesized. Compound 1f shows potent STS-inhibitory activity (IC = 1.

Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol.

The female hormone 17 β-estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its derivatives (1 and 2) were designed and synthesized as novel multitarget anticancer agents. Bissulfamate 1f exhibited potent STS-inhibitory activity and tubulin-polymerization-inhibitory activity.

Molecular epidemiological study of gammaherpesvirus in domestic cats in Japan.

Gammaherpesviruses (GHVs) are members of an emerging subfamily of the family Herpesviridae. A recent study identified a novel GHV in domestic cats (Felis catus GHV1, FcaGHV1), and epidemiological surveys have found that FcaGHV1 is distributed worldwide. In this study, we investigated the prevalence of GHVs in domestic cats in Japan with a molecular epidemiological survey.

Design and synthesis of iodocarborane-containing ligands with high affinity and selectivity toward ERβ.

The selectivity and the binding affinity of previously reported carborane-containing ligands 2 and 3 toward ERβ remains to be optimized. To improve their biological profiles, a series of iodinated carboranyl phenol derivatives (4-6) were designed and synthesized as prospective ERβ-selective ligands with high affinity. Several iodinated carboranyl phenols showed high relative binding affinity (RBA) values for both ERs, and especially for ERβ, due to suitable hydrophobic interactions of the iodine atoms with the hydrophobic amino acid residues of the ERβ ligand-binding domains.

Structure-activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties.

Amyloid-β aggregation inhibitors are expected to be therapeutic or prophylactic agents for Alzheimer's disease. Rosmarinic acid, which is one of the main aggregation inhibitors derived from Lamiaceae, was employed as a lead compound and its 25 derivatives were synthesized. In this study, the structure-activity relations of rosmarinic acid derivatives for the amyloid-β aggregation inhibitory effect (MSHTS assay), antioxidant properties, and xanthine oxidase inhibition were evaluated.

Effects of toceranib phosphate (Palladia) monotherapy on multidrug resistant lymphoma in dogs.

We examined whether multidrug resistant (MDR) canine lymphoma increases gene expression for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and c-KIT, and whether toceranib phosphate (TOC) has potential as a treatment for MDR canine lymphoma. The clinical data showed that PDGFRα expression was higher in canine subjects with MDR T-cell lymphoma than in those with untreated T-cell lymphoma, and that c-KIT expression was greater in subjects with T-cell lymphoma than in those with B-cell lymphoma. TOC monotherapy was well tolerated without serious adverse effects, and two of the five subjects that received TOC exhibited partial responses.

Inflammation-related microRNA expression level in the bovine milk is affected by mastitis.

MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR.

Detection and molecular characterization of Babesia, Theileria, and Hepatozoon species in hard ticks collected from Kagoshima, the southern region in Japan.

To reveal the distribution of tick-borne parasites, we established a novel nested polymerase chain reaction (PCR) system to detect the most common agents of tick-borne parasitic diseases, namely Babesia, Theileria, and Hepatozoon parasites. We collected host-seeking or animal-feeding ticks in Kagoshima Prefecture, the southernmost region of Kyusyu Island in southwestern Japan. Twenty of the total of 776 tick samples displayed a specific band of the appropriate size (approximately 1.

Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells.

The presence of tick-borne diseases in domestic dogs and cats living on Iriomote-jima and Tsushima islands.

The Iriomote cat and Tsushima leopard cat are endangered wildcats in Japan and inhabit only Iriomote-jima and Tsushima islands, respectively. Domestic dogs and cats living on Iriomote-jima and Tsushima islands were surveyed to clarify the interrelationship between wildcats and domestic animals regarding tick-borne disease transmission. Pathogen-derived DNA in blood samples was detected by polymerase chain reaction.