Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

CXCL5/CXCL8 induces neutrophilic inflammation in peri-implantitis.

OBJECTIVE AND BACKGROUND: This research aimed to examine the role of C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 8 (CXCL8; also known as IL-8) in neutrophilic inflammation triggered by peri-implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. MATERIALS: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri-implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3' mRNA-Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t-test was employed to conduct statistical analyses. RESULTS: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and CXCL5/CXCL8 was assessed via RT-qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p < .045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p < .008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri-implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning.

RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Use of neurofilament light chain to identify structural brain diseases in dogs.

BACKGROUND: Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. OBJECTIVES: To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. ANIMALS: Study included 37 healthy dogs, 31 dogs with idiopathic epilepsy (IE), 45 dogs with meningoencephalitis of unknown etiology (MUE), 20 dogs with hydrocephalus, and 19 dogs with brain tumors. METHODS: Cohort study. Serum NfL concentrations were measured in all dogs using single-molecule array technology. RESULTS: Serum NfL concentration in dogs with each structural disease was significantly higher than in healthy dogs and dogs with IE (P = .01). The area under the receiver operating characteristic curve of NfL for differentiating between dogs with structural diseases and IE was 0.868. An optimal cutoff value of the NfL 27.10 pg/mL had a sensitivity of 86.67% and a specificity of 74.19% to differentiate the dogs with IE from those with structural brain diseases. There were significant correlations between NfL concentrations and lesion size: (1) MUE, P = .01, r = 0.429; (2) hydrocephalus, P = .01, r = 0.563. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus.

Lipid Membrane Topographies Are Regulators for the Spatial Distribution of Liquid Protein Condensates.

Liquid protein condensates play important roles in orchestrating subcellular organization and as biochemical reaction hubs. Recent studies have linked lipid membranes to proteins capable of forming liquid condensates, and shown that biophysical parameters, like protein enrichment and restricted diffusion at membranes, regulate condensate formation and size. However, the impact of membrane topography on liquid condensates remains poorly understood. Here, we devised a cell-free system to reconstitute liquid condensates on lipid membranes with microstructured topographies and demonstrated that lipid membrane topography is a significant biophysical regulator. Using membrane surfaces designed with microwells, we observed ordered condensate patterns. Furthermore, we demonstrate that membrane topographies influence the shape of liquid condensates. Finally, we show that capillary forces, mediated by membrane topographies, lead to the directed fusion of liquid condensates. Our results demonstrate that membrane topography is a potent biophysical regulator for the localization and shape of mesoscale liquid protein condensates.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Quality Characteristics of Vegan Mayonnaise Produced Using Supercritical Carbon Dioxide-Processed Defatted Soybean Flour.

Emulsifiers, like egg yolk (EY), are necessary for the formation of mayonnaise, which is an oil-in-water type of colloid. This study aimed to assess the potential of defatted soybean powder treated with supercritical carbon dioxide (DSF) to enhance the quality of plant-based mayonnaise as plant-based alternatives gain popularity. This study involved the production of DSF and the comparison of its quality attributes to those of mayonnaise made with varying amounts of control soy flour (CSF), DSF, and EY. It was found that mayonnaise made with an increased quantity of DSF showed better emulsion stability, viscosity, and a smaller, more uniform particle size when compared with CSF mayonnaise. Additionally, DSF mayonnaise was generally rated higher in sensory evaluation. The addition of approximately 2% DSF positively influenced the emulsion and sensory properties of the vegan mayonnaise, indicating that DSF is a promising plant-based alternative emulsifier for the replacement of animal ingredients.

Identification of novel dimers and chemical profiling of acid amide alkaloids in Piper nigrum.

Peppers (Piper nigrum L.) are distinguished by their pungent flavor and aroma. Piperine is a major acid-amide alkaloid with a piperidine ring that gives pepper its flavor and scent. In plant metabolomics research, the accessibility of the chemical standards is critical for scientific credibility. We isolated and identified 10 novel dimers of acid amide alkaloids (9-15 and 20-22), along with 12 known monomers (1-6) and dimers (7, 8, 16-19) from black pepper. Subsequently, we found the distribution of monomers and dimers of acid amide alkaloids in black and white peppers by twenty-two acid amide alkaloids which we obtained using the molecular networking technique and multivariate analysis to reveal the molecular relationships between the acid amide alkaloids in black and white peppers. Our research delved into the chemical diversity of acid amide alkaloids in black and white peppers, which could help inform future culinary and potential medicinal utilization of pepper.

Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography.

PURPOSE: Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels. PROCEDURES: All animals utilized in this study were male Sprague-Dawley (SD) rats weighing between 250 and 300 g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16 min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine. RESULTS: Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16 min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32 min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45 µmol (15 mM, 30 µL) and 0.75 µmol (15 mM, 50 µL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement. CONCLUSION: In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.

Diffusion time-related structure-function coupling reveals differential association with inter-individual variations in body mass index.

Body mass index (BMI) is an indicator of obesity, and recent neuroimaging studies have demonstrated that inter-individual variations in BMI are associated with altered brain structure and function. However, the mechanism underlying the alteration of structure-function correspondence according to BMI is under-investigated. In this study, we studied structural and functional connectivity derived from diffusion MRI tractography and inter-regional correlations of functional MRI time series, respectively. We combined the structural and functional connectivity information using the Riemannian optimization approach. First, the low-dimensional principal eigenvectors (i.e., gradients) of the structural connectivity were generated by applying diffusion map embedding with varying diffusion times. A transformation was identified so that the structural and functional embeddings share the same coordinate system, and subsequently, the functional connectivity matrix was simulated. Then, we generated gradients from the simulated functional connectivity matrix. We found the most apparent cortical hierarchical organization differentiating between low-level sensory and higher-order transmodal regions in the middle of the diffusion time, indicating that the hierarchical organization of the brain may reflect the intermediate mechanisms of mono- and polysynaptic communications. Associations between the functional gradients and BMI were strongest when the hierarchical structure was the most evident. Moreover, the gradient-BMI association map was related to the microstructural features, and the findings indicated that the BMI-related structure-function coupling was significantly associated with brain microstructure, particularly in higher-order transmodal areas. Finally, transcriptomic association analysis revealed the potential biological underpinnings specifying gene enrichment in the striatum, hypothalamus, and cortical cells. Our findings provide evidence that structure-function correspondence is strongly coupled with BMI when hierarchical organization is the most apparent and that the associations are related to the multiscale properties of the brain, leading to an advanced understanding of the neural mechanisms related to BMI.

GAN-MAT: Generative adversarial network-based microstructural profile covariance analysis toolbox.

Multimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT.

Beneficial Effect of Rapamycin on Liver Fibrosis in a Mouse Model (C57bl/6 Mouse).

BACKGROUND: Liver fibrosis is a chronic inflammatory disease that progresses and has a high mortality rate. This study was performed to investigate the protective effect of rapamycin on experimentally induced chronic liver injury in mice models using both biochemical parameters of liver function enzymes. METHODS: Twenty-four mice were divided randomly into 4 equal groups: [1] the normal group, n = 6; [2] the liver fibrosis (LF) group, n = 6; [3] the LF with the treatment of rapamycin group, n = 6; [4] the LF with the treatment of silimaryn, n = 6. RESULTS: In the group receiving oral administration of rapamycin, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine were found to significantly decrease compared to the liver fibrosis group. Rapamycin, in the orally administered group, demonstrated a statistically significant decrease in the expression of interleukin (IL) 10, IL-1B, inducible nitric oxide synthase, and tumor necrosis factor alpha compared to the liver fibrosis group. CONCLUSIONS: In this study, we explored the potential therapeutic effects of rapamycin on liver fibrosis in an animal model.

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Oesophageal stricture in a cat with true pleuroperitoneal hernia.

A 2-year-old neutered male Bengal cat presented with solid food dysphagia and chronic regurgitation for >5 months. There were no clinical abnormalities on haematological or radiographic examinations. Thoracic radiography revealed a soft tissue opacity mass adjacent to the diaphragm in the caudoventral thorax. Ultrasonography revealed a protruding liver lobe surrounded by a hyperechoic lining from the diaphragm towards the thorax, and a pleuroperitoneal hernia was diagnosed. An endoscopy was performed to examine the cause of regurgitation, and an oesophageal stricture was observed. Endoscopic balloon dilation of the oesophageal stricture was performed, and the regurgitation was resolved immediately. However, regurgitation relapsed 2 months later, and computed tomography was performed to ascertain the cause. Computed tomography revealed oesophageal mural thickening and true pleuroperitoneal hernia with partial liver lobe herniation. A second endoscopy with balloon dilation was performed to treat the relapsing oesophageal stricture, and the clinical signs resolved without the need for herniorrhaphy. Nevertheless, oesophageal stricture could occur due to gastroesophageal reflux related to a pleuroperitoneal hernia; however, a definite link could not be elucidated in this case. This report describes a case of oesophageal stricture and concurrent true pleuroperitoneal hernia in a cat.

An evaluation of the physiological uptake range of 18F-fluoro-2-deoxy-D-glucose in normal ovaries of seven dogs using positron emission tomography/computed tomography.

Introduction: This study evaluated the physiological uptake range of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in the normal ovaries of seven dogs using positron emission tomography/computed tomography (PET/CT). Materials and methods: The dogs were subjected to general anesthesia and were positioned in ventral recumbency for PET/CT scans. The dosage of 18F-FDG ranged from 0.14 to 0.17 mCi/kg and was administered intravenously followed by 0.9% NaCl flushing; PET/CT images of each dog were obtained precisely 60 min after the injection of 18F-FDG. The regions of interest were drawn manually, and standardized uptake values (SUV) were calculated to evaluate the 18F-FDG uptake in each ovary. The maximum and mean SUVs (SUV max and SUV mean) for all the ovaries of the dogs were then computed. Results: The range of SUV max and SUV mean of the normal ovaries of the dogs were 1.28-1.62 and 1.07-1.31 (mean ± standard deviation), respectively. Conclusion: This is the first study to investigate the normal 18F-FDG uptake baseline data of normal canine ovaries using PET/CT scans. These data will help clinicians in identifying malignant tumors before anatomical changes in the ovary through PET/CT scans.

Serum concentrations of complement C3 and C4 in dogs with idiopathic epilepsy.

BACKGROUND: High concentrations of complement factors are presented in serum of animal epilepsy models and human patients with epilepsy. OBJECTIVES: To determine whether complement dysregulation occurs in dogs with idiopathic epilepsy (IE). ANIMALS: The study included 49 dogs with IE subgrouped into treatment (n = 19), and nontreatment (n = 30), and 29 healthy dogs. METHODS: In this case-control study, the serum concentrations of the third (C3) and fourth (C4) components of the complement system were measured using a canine-specific ELISA kit. RESULTS: Serum C3 and C4 concentrations were significantly higher in dogs with IE (C3, median; 4.901 [IQR; 3.915-6.673] mg/mL, P < .001; C4, 0.327 [0.134-0.557] mg/mL, P = .03) than in healthy control dogs (C3, 3.550 [3.075-4.191] mg/mL; C4, 0.267 [0.131-0.427] mg/mL). No significant differences were observed in serum C3 and C4 concentrations between dogs in the treatment (C3, median; 4.894 [IQR; 4.192-5.715] mg/mL; C4, 0.427 [0.143-0.586] mg/mL) and nontreatment groups (C3, 5.051 [3.702-7.132] mg/mL; C4, 0.258 [0.130-0.489] mg/mL). Dogs with a seizure frequency >3 times/month had significantly higher serum C3 (6.461 [4.695-8.735] mg/mL; P < .01) and C4 (0.451 [0.163-0.675] mg/mL; P = .01) concentrations than those with a seizure frequency ≤3 times/month (C3, 3.859 [3.464-5.142] mg/mL; C4, 0.161 [0.100-0.325] mg/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: Dysregulation of classical complement pathway was identified in IE dogs. Serum C3 and C4 concentrations could be diagnostic biomarkers for IE in dogs with higher seizure frequency.

A single-blind randomised study comparing the efficacy of fluconazole and itraconazole for the treatment of Malassezia dermatitis in client-owned dogs.

BACKGROUND: No reports have compared the clinical therapeutic efficacy of fluconazole and itraconazole in canine Malassezia dermatitis. OBJECTIVES: The study aimed to compare the clinical therapeutic efficacy of fluconazole and itraconazole and to evaluate the adverse effects of fluconazole in canine Malassezia dermatitis. ANIMALS: Sixty-one client-owned dogs with Malassezia dermatitis. MATERIALS AND METHODS: The enrolled animals were randomly divided into groups receiving 5 mg/kg fluconazole (5FZ), 10 mg/kg fluconazole (10FZ) or 5 mg/kg itraconazole (5IZ). The drugs were orally administered once daily for 28 days. Cytological examination, clinical index score (CIS), pruritus Visual Analog Scale (PVAS) evaluation and blood analysis (for 5FZ only) were performed on Day (D)0, D14 and D28. RESULTS: On D14, significant reductions in mean yeast count (MYC), CIS and PVAS were observed in the 5FZ (n = 20, p < 0.01), 10FZ (n = 17, p < 0.01) and 5IZ (n = 16, p < 0.05) groups. In all three groups, a significant reduction (p < 0.001) in MYC, CIS and PVAS expression was observed on D28. There was no significant difference in the percentage reduction of MYC, CIS and PVAS among the groups. Moreover, there was a significant difference (p < 0.05) in each group between D14 and D28, except for the percentage reduction in MYC in the 10FZ and 5IZ groups. No adverse effects of fluconazole were observed in the 5FZ or 10FZ groups. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that 5FZ and 10FZ are as effective as itraconazole in canine Malassezia dermatitis.

Expression of sphingosine-1-phosphate receptor 1 in neuroinflammation of canine brains.

Sphingosine-1-phosphate (S1P) is a signaling lipid mediator that is involved in multiple biological processes. The S1P/S1P receptor (S1PR) signaling pathway has an important role in the central nervous system. It contributes to physiologic cellular homeostasis and is also associated with neuroinflammation. Therefore, this study was performed to evaluate the expression of S1PR in dogs with meningoencephalitis of unknown etiology (MUE) and experimental autoimmune encephalomyelitis (EAE). The analysis used 12 brain samples from three neurologically normal dogs, seven dogs with MUE, and two canine EAE models. Anti-S1PR1 antibody was used for immunohistochemistry. In normal brain tissues, S1PR1s were expressed on neurons, astrocytes, oligodendrocytes, and endothelial cells. In MUE and EAE lesions, there was positive staining of S1PR1 on leukocytes. Furthermore, the expression of S1PR1 on neurons, astrocytes, oligodendrocytes, and endothelial cells was upregulated compared to normal brains. This study shows that S1PR1s are expressed in normal brain tissues and leukocytes in inflammatory lesions, and demonstrates the upregulation of S1PR1 expression on nervous system cells in inflammatory lesions of MUE and EAE. These findings indicate that S1P/S1PR signaling pathway might involve physiologic homeostasis and neuroinflammation and represent potential targets for S1PR modulators to treat MUE.

Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway.

Oral squamous cell carcinoma (OSCC) is a prevalent oral and maxillofacial cancer with high mortality as OSCC cells readily invade tissues and metastasize to cervical lymph nodes. Although imatinib exhibits potential anticancer and remarkable clinical activities that therapeutically affect several cancer types, its specific impact on OSCC has yet to be fully explored. Therefore, this study investigated the potential anticancer effect of imatinib on OSCC cells and the underlying mechanisms. The Cell Counting Kit-8 was used to determine the impact of imatinib on cell viability. Then, morphological cell proliferation analysis was conducted to examine how imatinib impacted OSCC cell growth. Moreover, OSCC cell migration was determined through wound-healing assays, and colony formation abilities were investigated through the soft agar assay. Lastly, the effect of imatinib on OSCC cell apoptosis was verified with flow cytometry, and its inhibitory mechanism was confirmed through Western blot. Our results demonstrate that imatinib effectively inhibited OSCC cell proliferation and significantly curtailed OSCC cell viability in a time- and concentration-dependent manner. Furthermore, imatinib suppressed migration and colony formation while promoting OSCC cell apoptosis by enhancing p53, Bax, and PARP expression levels and reducing Bcl-2 expression. Imatinib also inhibited the PI3K/AKT/mTOR signaling pathway and induced OSCC cell apoptosis, demonstrating the potential of imatinib as a treatment for oral cancer.