Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. METHODS: Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. RESULTS: Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. CONCLUSIONS: This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib.

Background: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods: Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, ß-catenin. Hepatocyte growth factor receptor (C-MET/HGFR) and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a quantitative sandwich enzyme immunoassay technique. Results: Inhibition of AURK reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was very low in both DEN-induced and anti- AURK groups respectively. The hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear INCENP whereas in anti- AURK markedly decreased. Expression of ß-catenin, NF-kB and c-Jun did not differ in liver tumors of both AURK -depleted and non-depleted mice. Conclusions: Depletion of AURK reduced the number of DEN-induced hepatic tumours. However, their size did not differ significantly between the groups.

Corrigendum to "Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar".

[This corrects the article DOI: 10.1155/2016/9010279.].

Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar.

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

Effects of central sympathetic activation on repolarization-dispersion during short-term myocardial ischemia in anesthetized rats.

AIMS: Sympathetic activation during myocardial ischemia enhances arrhythmogenesis, but the underlying pathophysiologic mechanisms remain unclear. We investigated the central sympathetic effects on ventricular repolarization during the early-period post-coronary artery occlusion. MAIN METHODS: We studied 12 Wistar rats (254±2 g) for 30 min following left coronary artery ligation, with (n=6) or without (n=6) pretreatment with the central sympatholytic agent clonidine. Mapping of left and right ventricular epicardial electrograms was performed with a 32-electrode array. As an index of sympathetic activation, heart rate variability in the frequency domain was calculated. Heart rate and repolarization duration were measured with a custom-made recording and analysis software, followed by calculation of intra- and inter-ventricular dispersion of repolarization. KEY FINDINGS: Heart rate and heart rate variability indicated lower sympathetic activation in clonidine-treated rats during ischemia. Repolarization duration in the left ventricle prolonged after clonidine at baseline, independently of heart rate, but no differences were present 30 min post-ligation. Dispersion of repolarization in the right ventricle remained stable during ischemia, whereas it increased in the left ventricle, equally in both groups. A similar trend was observed for inter-ventricular dispersion, without differences between groups. SIGNIFICANCE: In addition to intra-ventricular repolarization-dispersion, anterior-wall myocardial ischemia may also increase inter-ventricular repolarization-dispersion. Progressive central sympathetic activation occurs during myocardial ischemia, but it does not affect intra- or inter-ventricular dispersion of ventricular repolarization during the early phase. Further research is warranted on the potential effects during subsequent time-periods.

Effects of U-74389G (21-Lazaroid) and Ascorbic Acid on Liver Recovery After Acute Ischemia and Reperfusion in Rats.

BACKGROUND/AIM: The free radical-scavenging effects of the lazaroid U-74389G have been shown in several experimental models to protect the liver from ischemia/reperfusion (I/R), however, the mechanism of cytoprotection is not fully understood. Similar findings were observed when ascorbic acid was administered. This study investigates the effects of infusion of lazaroid U-74389G and ascorbic acid on cytokines and liver structure in a liver I/R rat model. MATERIALS AND METHODS: Sixty male Wistars rats, weighting 220-290 g, were used in the study. Six experimental groups were formed: Group 1 (control group): ischemia for 30 min and reperfusion for 60 min; group 2 (control group): ischemia for 30 min and reperfusion for 120 min; group 3: ischemia for 30 min, intraportal injection of ascorbic acid, and reperfusion for 60 min; group 4: ischemia for 30 min, ascorbic acid administration, and reperfusion for 120 min; group 5: ischemia for 30 min, U-74389G administration, and reperfusion for 60 min; and group 6: ischemia for 30 min, U-74389G administration, and reperfusion for 120 min. Tissue and blood sampling took place upon completion of each model's reperfusion. U-74389G was administered at 10 mg/kg animal body weight and ascorbic acid at 100 mg/kg. Anesthesia was induced with ketamine and xylazine. Surgery was performed through a midline laparotomy. The portal vein and the common hepatic artery were isolated and prepared for occlusion. Blood samples and wedge liver biopsies were taken to measure levels of liver enzymes, cytokines and for microscopic analysis upon completion of reperfusion once for each model. RESULTS: Histopathological evaluation revealed a statistically significant reduction in the degree of necrosis of liver tissue in the treated groups compared to the control groups 1 and 2 [groups 3, 5 (p=0.010) and 4, 6 (p<0.0005)]. On the other hand, tissue malondialdehyde levels (MDA) were statistically significantly increased only between control group 2 and groups 4, 6 (p<0.0005). There was no statistically significant difference in tumor necrosis factor-α between groups. As for liver enzymes, only alkaline phosphatase (ALP) and gamma-glutamyl transferase (gGT) were statistically significantly reduced in treated groups 3 and 5 (ALP: p=0.027, and gGT: p=0.002) and 4 and 6 (ALP: p=0.004, and gGT: p=0.015) compared to control groups 1 and 2. CONCLUSION: Based on histological data and the reduction of some of the liver enzymes, in spite of a rise of malondialdehyde, in this rat model, administration of U-74389G in liver ischemia/reperfusion (I/R) injury has potential in attenuating liver damage.