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BackgroundThe intraventricular pressure difference (IVPD) and intraventricular pressure gradients (IVPG), estimated from color M-mode echocardiography (CMME) of the transmitral flow, have been introduced as novel indices for the evaluation of heart functions. Until now, no study demonstrated the feasibility of the CMME approach to measure IVPD and IVPG in any farm animals. The aim of this study was to assess the feasibility and repeatability of CMME-derived IVPD and IVPG variables in goats and explore the effect of sedation on the measured variables.Materials and methodsSixteen male Shiba goats were included in this study and underwent conventional echocardiography. Eight goats were used in the repeatability of IVPD/IVPG variables. Another eight goats were used to evaluate the effect of sedation by xylazine on IVPD/IVPG measurements. CMME between the base and the apex of the left ventricle was carried out. The IVPD and IVPG were analyzed using in-house code software. The IVPD and IVPG were expressed as total, basal, mid-to-apical, mid, and apical segments. Data analysis including the imaging quality score (IQS), repeatability, variability, intraclass correlation coefficient (ICC), as well as the effect size of sedation on the measured variables was calculated.ResultsIVPD and IVPG variables from CMME were feasible in all goats. Low to moderate variability of IVPD and IVPG variables was observed (CV 95% <25%) except for the apical IVPD and apical IVPG. The IVPD/IVPG measurements were repeatable without a significant effect of animal or time on the obtained measurements. The overall ICC was higher than 0.75 in all variables except for the apical segment. Xylazine administration reduced the total, basal, and mid parts of IVPD and IVPG with a large effect size (biserial ranked correlation; rc > 0.8).ConclusionWe reported, for the first time, IVPD and IVPG measurements by CMME in goats. The assessment of IVPD and IVPG by CMME is feasible in goats which can be evaluated in further cardiovascular or pharmacological studies in this species.

Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC.