The pet industry, especially pet food, is experiencing rapid growth. This growth is accompanied by increasing concerns about pets' gut health, as an imbalanced microbiota can lead to various diseases. This study analyzes global patent trends in microbiome-based technologies for treating pet digestive issues using the WIPS database across major markets. Of 1,194 patents identified, 394 key references were examined, highlighting the increasing number of probiotic and microbiome-related patents since 2016. China dominates this sector, followed by Korea, Japan, and the United States. The findings provide a foundation for advancing microbiome-driven solutions for pet digestive ailments.
Traditional medicine and herbal remedies are gaining popularity worldwide, comprising a significant portion of healthcare research, advancements, and market demand. Growing scientific evidence supports their substantial efficacy as pharmaceutical ingredients and dietary supplements in preventive healthcare. When developing pharmaceuticals, it is crucial to ensure that ingredients are free from side effects and toxicity in order to prioritize safety. Geckos, known as shou gong, are a diverse group of lizards that are widely utilized for treating various diseases in Korean Medicine. This study was conducted to assess the potential acute toxicity of a water extract Gekko gecko by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups (5 rats each). Test articles were administrated once by oral gavage to rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg body weight. Mortality, changes of body weight, and clinical signs of gross observation were monitored for 14 days after dosing. At the end of a 14-day observation period, all animals were sacrificed and complete macroscopic and hematological examinations were performed. There was no dead animal or test article-related effect on clinical signs, body weight, or gross finding. Other specific changes were not found between control and treated groups in hematology. Results showed no adverse effect at a dose of 500, 1,000, or 2,000 mg/kg in rats. The minimal lethal dose was considered to be over 2,000 mg/kg body weight in rats.
Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.
This study was conducted to collect the patents of microbiome-based treatment technology for pets. An electronic search for microbiome or probiotics in brain nervous system disease was studied using the WINTELIPS database. Patent Cooperation Treaty of Korea, Japan, the EU, the US, and China that were registered by October 31, 2022 were selected in this study. A total of 206 patents were included for final analysis. Since 2016, patent activity has shown an explosive increase in recent years. China is the leading market in this technology field, and Korea has the second-highest market share. To provide the groundwork for the next research and development, we examined the industrial trend of microbiome for brain nervous system diseases in this study using an analysis of patents that have been applied for and registered up to this point. Looking at the overall patent trends by year in the technology field related to treating of brain and nervous system diseases using the microbiome, there was a tendency to repeat increasing and decreasing trends. However, considering 2021 and 2022, which have undisclosed sections, it can be seen that patent activity has tended to increase explosively in recent years, starting in 2016. If related studies use the patent analysis data constructed in this way strategically, it is expected that it will lead to patent registration and the development of new products, ultimately contributing to the revitalization of the companion animal industry.
Collagen peptides have garnered significant attention as functional foods across multiple fields due to their capacity to regulate physiological and hormonal processes, offering numerous advantages. However, despite their broad range of applications, comprehensive research on the potential toxicity of these substances remains lacking. Therefore, this study sought to assess the acute oral toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in both rats and dogs. In the rat model, CPSS was orally administered at doses of 300 and 2,000 mg/kg to Sprague-Dawley rats. An escalating single-dose oral toxicity assessment at doses of 500, 1,000, and 2,000 mg/kg was carried out in beagle dogs with 3-day intervals between doses. Throughout the 14-day post-administration assessment period, clinical signs, mortality rates, changes in body weight, and necropsy observations were closely monitored. After oral administration, no signs of toxicity associated with CPSS were observed in either rats or dogs. Therefore, the oral LD50 (approximate lethal dose for 50% mortality) for CPSS in rats was determined to exceed 5,000 mg/kg, and the maximum tolerated dose for dogs was estimated to be above 2,000 mg/kg. Consequently, this study offers safety data on the use of CPSS in functional foods and medicinal applications.
Fermentation by Rhizopus spp. has been used as a traditional medicine for treating various inflammatory diseases. Allergic asthma is a chronic respiratory disease that is caused by an exaggerated immune response. This study was conducted to ascertain the anti-inflammatory effects of Rhizopus spp. fermentation extract (RU) on a mouse model of ovalbumin (OVA)-induced asthma. The animals were intraperitoneally injected OVA on day 1 and 7, followed by OVA intranasal inhalation on days 14 to 18. The animals were treated daily with RU (100 and 200 mg/kg) by oral gavage from day 18 to day 23. RU significantly decreased eosinophilia and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with reducing airway inflammation and mucus secretion in lung tissue. Histological changes in the lungs and levels of inflammatory mediators of allergic airway inflammation were evaluated. The regulatory effects of RU on type 2 helper T (Th2) cell activation were investigated. RU administration attenuated asthmatic changes such as inflammatory cell infiltration and mucus production, decreased the levels of Th2-related cytokines, and reduced Th2 cell activation. Administration of RU effectively reduced allergic responses in asthmatic mice, which is associated with regulating Th2 cell activation and differentiation. These results indicate that RU can attenuate the respiratory symptoms of asthma.
The vomeronasal organ (VNO) is critical for reproduction and social behavior in ruminants, including cattle. The present study examined the structure of the VNO and its epithelial cells in neonatal and adult Korean native cattle (Hanwoo), Bos taurus coreanae , using immunohistochemistry and lectin histochemistry. Histologically, the VNO comprised two types of epithelia: medial vomeronasal sensory (VSE) and lateral vomeronasal non-sensory epithelia (VNSE). Numerous blood vessels and nerve bundles were observed within the vomeronasal cartilage encased lamina propria. Immunohistochemistry revealed high expression level of protein gene product9.5 and moderate expression level of olfactory marker protein in the neuroreceptor cells of the VSE and occasionally in some ciliated cells of the VNSE in both neonates and adults. The properties of the glycoconjugates in the VNO were investigated using 21 lectins, most of which were expressed at varied intensities in the VSE and VNSE, as well as in the lamina propria. Several lectins exhibited variations in their intensities and localization between neonatal and adult VNOs. This study is the first descriptive lectin histochemical examination of the VNO of Korean native cattle with a focus on lectin histochemistry, confirming that the VNO of Korean native cattle is differentiated during postnatal development.
Celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, was approved as a non-steroidal anti-inflammatory drug (NSAID), and this therapeutic application has been expanded to several other diseases, including colon cancer. Notably, a treatment strategy combining the use of celecoxib and radiation therapy has been employed for improving the control of local cancers. In this study, we examined the effect of celecoxib on irradiation-induced intestinal damage. The twenty four mice (BALB/c) were divided into four groups; 1) sham-irradiated control group, 2) celecoxib-treated group, 3) irradiated group, and 4) celecoxib-treated irradiation group. Mice were orally administered celecoxib at a dose of 25 mg/kg in a 0.1 mL volume, daily for 4 days after irradiation exposure (10 Gy). Then, histological examinations of the jejunal villous height, crypt survival, and crypt size were performed. The expression of COX-2 after administration of celecoxib in irradiated mice was examined by employing immunohistochemistry, Western blotting, and qPCR analysis. The jejunal villi height and the crypt survival were reduced in the irradiation group compared with the sham-irradiated group. Celecoxib treatment in irradiation mice even more decreased those indicators. Crypt size was increased in the radiation group compared to the sham-irradiated control group, whereas the size was decreased in the celecoxibtreated irradiation group compared with the group exposed to the radiation injury. COX-2 expression was detected in the crypt of the small intestine, and COX-2 expression was increased in the crypt lesion following radiation exposure. However, COX-2 expression was reduced in the celecoxib-treated irradiation group. Therefore, in the present study, we confirmed that celecoxib treatment after irradiation aggravated the irradiation-induced intestinal damage. These results suggest that a caution need to be administered when celecoxib treatment is performed in combination with radiation therapy for cancer treatment.