Background: Betulinic acid (BA) is a complex lupane triterpenoid with unique antineoplastic activity. However, its antiproliferative activity is far from satisfaction. In order to improve its anticancer efficacy, betulinic acid was conjugated with a nitric oxide (NO)-releasing moiety to get a novel hybrid, BA-78. Methods: The antiproliferative activity of BA-78 against 6 cell lines and the ability of releasing nitric oxide were determined. The pro-apoptosis mechanism of BA-78 was investigated as well. Results: BA-78 exhibited time-dependent release of NO, and it displayed higher antiproliferative potential than BA through increasing apoptosis and inducing cell cycle arrest at G1 phase. Western blotting results showed that BA-78 increased the expression of Bax, Bid, Bad and cytochrome C and reduced the level of anti-apoptosis proteins including Bcl-2 and Bcl-xl. Conclusion: Our study revealed that novel compound BA-78, possessing betulinic acid and nitric oxide (NO)-releasing moiety, could be developed as an antitumor agent.

In recent years, multilevel spinal cord injuries (SCIs) have gained a substantial amount of attention from clinicians and researchers. Multilevel noncontinuous SCI patients cannot undergo the multiple steps of a one-stage operation because of a poor general condition or a lack of proper surgical approaches. The surgeon subsequently faces the decision of whether to initially relieve the rostral or caudal compression. In this study, we established a spinal cord compression model involving two noncontinuous segments in rabbits to evaluate the effects of differences in decompression order on the functional recovery of the spinal cord. A Fogarty catheter was inserted into the epidural space through a hole in T6-7 and advanced 3 cm rostrally or caudally. Following successful model establishment, which was demonstrated by an evaluation of evoked potentials, balloons of different volumes (40 μl or 50 μl) were inflated in the experimental groups, whereas no balloons were inflated in the control group. The experimental groups underwent the first decompression in the rostral or caudal area at 1 week post-injury; the second decompression was performed at 2 weeks post-injury. For 6 weeks post-injury, the animals were tested to determine behavioral scores, somatosensory evoked potentials (SEPs) and radiographic imaging changes; histological and apoptosis assay results were subsequently analyzed. The behavioral test results and onset latency of the SEPs indicated that there were significant differences between priority rostral decompression (PRD) and priority caudal decompression (PCD) in the 50-μl compression group at 6 weeks post-injury; however, there were no significant differences between the two procedures in the 40-μl group at the same time point. Moreover, there were no significant peak-to-peak amplitude differences between the two procedures in the 50-μl compression group. The findings of this study suggested that preferential rostral decompression was more beneficial than priority caudal decompression with respect to facilitating spinal cord functional recovery in rabbits with severe paraplegia and may provide clinicians with a reference for the clinical treatment of multiple-segment spinal cord compression injuries.

Background: Severe liver diseases, such as liver fibrosis, cirrhosis, and liver cancer, are mainly caused by hepatitis B virus (HBV). This study investigated the differences between gut microbiota in HBeAg-positive and negative groups of patients with chronic hepatitis B (CHB) and investigated the effect of tenofovir alafenamide (TAF) on gut microbiota.Methods: This prospective study included patients with CHB not taking nucleoside antivirals (No-NAs group, n = 95) and those taking TAF (TAF group, n = 60). We divided CHB patients into two groups according to the HBeAg status of the subjects on the day of data collection. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients. We investigated the improvement of clinical symptoms by TAF, as well as differences in gut microbiota between different groups by 16S rRNA high-throughput sequencing.Results: Gut microbiota demonstrated significant differences between patients with HBeAg-positive and -negative CHB. Both the No-NAs and TAF Phase 2 subgroups demonstrated significantly increased microbiota richness and diversity, showing greater heterogeneity. Additionally, the Phase 2 subgroup exhibited a low abundance of pathways associated with glucose metabolism and amino acid metabolism. The TAF group demonstrated a significantly decreased HBV load, alanine aminotransferase, and aspartate aminotransferase and a significant increase in prealbumin compared with the No-NAs group. No significant difference was found in uric acid, creatinine, blood calcium, inorganic phosphorus, eGFR, and β2-microglobulin concentrations between the two groups. Additionally, the urea level in the TAF group was significantly lower than that in the No-NAs group, but with no significant effect on other indicators such as eGFR and β2-microglobulin.Conclusion: This study revealed significant differences in gut microbiota composition and function between patients with HBeAg-positive and -negative CHB.