Ginsenoside Rg3 (Rg3) has been studied in several cancer models and is suggested to act through various pharmacological effects. We investigated the anticancer properties of Rg3 through myeloid-derived suppressor cell (MDSC) modulation in FM3A mouse mammary carcinoma cells. The effects of Rg3 on MDSCs and consequent changes in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) were evaluated by diverse methods. MDSCs promoted cancer by enhancing breast cancer stemness and promoting EMT. Rg3 at a dose without obvious cytotoxicity downregulated MDSCs and repressed MDSC-induced cancer stemness and EMT. Mechanistic investigations suggested that these inhibitory effects of Rg3 on MDSCs and corresponding cancer progression depend upon suppression of the STAT3-dependent pathway, tumor-derived cytokines, and the NOTCH signaling pathway. In a mouse model, MDSCs accelerated tumor progression, and Rg3 delayed tumor growth, which is consistent with the results of in vitro experiments. These results indicated that Rg3 could effectively inhibit the progression of breast cancer. The anticancer effect of Rg3 might be partially due to its downregulation of MDSCs and consequent repression of cancer stemness and EMT in breast cancer. Hence, we suggest the regulation of MDSCs through Rg3 treatment as an effective therapeutic strategy for breast cancer patients.

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species and 114 metabolites from the gutMgene database. Further, we used different online-based database platforms to predict 1890 gene targets associated with metabolites. Moreover, DisGeNET, OMIM, and Genecard databases were used to consider 13,104 disease-related gene targets. We used a Venn diagram and various protein−protein interactions (PPIs), KEGG pathways, and GO analyses for the functional analysis of gene targets. Moreover, the subnetwork of protein−protein interactions (through string and cytoscape platforms) was used to select the top 20% of gene targets through degree centrality, betweenness centrality, and closeness centrality. To screen the possible candidate compounds, we performed an analysis of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of metabolites and then found the best binding affinity using molecular docking simulation. (3) Results: Finally, we found the key gene targets that interact with suitable compounds and function against kidney cancer and inflammation, such as MTOR (with glycocholic acid), PIK3CA (with 11-methoxycurvularin, glycocholic acid, and isoquercitrin), IL6 (with isoquercitrin), PTGS2 (with isoquercitrin), and IGF1R (with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, isoquercitrin), showed a lower binding affinity. (4) Conclusions: This study provides evidence to support the positive effects of SCFA-producing microbial metabolites that function against kidney cancer and inflammation and makes integrative research proposals that may be used to guide future studies.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE’s mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography–mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERβ, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/β-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

Background: Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that granulomatous meningoencephalomyelitis (GME) and necrotizing encephalomyelitis (NE) are similar to multiple sclerosis (MS), which is a human autoimmune demyelinating central nervous system disease. Objectives: Considering this perspective, we hypothesized that canine GME and NE have significant expression of one or more TKs, which are associated with human MS pathogenesis. Methods: To determine the possible use of conventional multi-targeted TKIs as a treatment for canine GME and NE, we characterized the immunohistochemical expression of platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-ss, vascular endothelial growth factor receptor (VEGFR)-2, c-Abl and c-Kit in GME and NE samples. Results: Histological samples from four dogs with GME and three with NE were retrieved. All samples stained positive for PDGFR-ss (7/7 [100%]). PDGFR-alpha and c-Kit were expressed in 3/7 (42.8%) samples each. c-Abl was identified in 2/7 (28.5%) samples; no sample showed VEGFR-2 (0%) expression. Co-expression of TKs was identified in 6/7 (85.7%) dogs. Conclusions All samples were positive for at least one or more of PDGFR-alpha, PDGFR-ss, c-Kit and c-Abl, which are known as the target TKs of conventional multi-targeted TKIs. Their presence does suggest that these TKs may play a role in the pathogenesis of GME and NE. Therefore, multi-targeted TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs.

Snake envenomation is a medical emergency capable of causing local and systemic complications. However, information on venomous snakebite in dogs in South Korea is scarce. In this study, fifty-nine dogs treated at a private veterinary clinic from 2004 to 2021 were retrospectively studied. The aim was to characterize the demographics, elapsed time between snakebite and veterinary clinic presentation, laboratory findings, clinical signs, treatments, adverse reactions to antivenom, and prognosis of venomous snakebite. Snakebite was mostly observed between 12 p.m. and 5 p.m. from April to October. On the days of envenomation, the weather conditions were mostly cloudy, followed by rain/precipitation, and least frequently fair weather. Grassland was the most common incident location, and leashed dog walking was the most frequent activity when snakebite occurred. The main local symptoms were edema, hemorrhagic discharge, cutaneous erythema, ulceration, and necrosis. Major systemic clinical signs were tachypnea, tachycardia, altered mentation, ptyalism, and hypotension. Based on the time interval between snakebite and presentation at the veterinary clinic, two groups were defined: <4 h (Group 1, 49.2%) and ≥4 h (Group 2, 50.8%). Systemic inflammation was more frequently observed in Group 2. The level of C-reactive protein at presentation (p = 0.036) and the highest-level during hospitalization (p = 0.023) were significantly elevated in Group 2 (≥4 h). The dogs in Group 2 displayed more frequent muscle damage (increased creatine kinase) than the dogs in Group 1, and a higher level of creatine kinase was associated with delayed (≥4 h) presentation after snakebite (p = 0.003). All of the dogs were treated symptomatically, and 34 dogs (58%) received antivenom. Treatment with antivenom showed no adverse reactions in this study. All of the treated dogs recovered. One dog was euthanized without any treatment due to respiratory distress, hypotension, and cost constraints. In conclusion, this study provides baseline information on venomous snakebite in dogs in South Korea. The prognosis was excellent, especially when the dogs were treated within 4 h.