The coumarin component isofraxidin targets the G-protein-coupled receptor S1PR1 to modulate IL-17 signaling and alleviate ulcerative colitis.

OBJECTIVE: The increasing global prevalence of ulcerative colitis (UC) underscores the imperative to explore novel therapeutic approaches. Traditional Chinese medicine has historically shown potential in addressing this ailment. The current study aimed to elucidate the functional attributes and underlying mechanisms of isofraxidin, a coumarin derivative from Acanthopanax, in the context of UC. METHODS: A murine model of dextran sodium sulfate (DSS)-induced UC was established, and we conducted a comprehensive assessment of the influence of isofraxidin on UC symptomatology, colonic histopathological manifestations, the inflammatory response, and apoptosis. The potential receptor of isofraxidin was initially identified through the Target database and molecular docking analysis. Subsequent in vivo and in vitro experiments were conducted to determine the effects of isofraxidin on the identified receptor and associated signaling pathways. Transfection was used to examine the receptor's role in the regulatory mechanism of isofraxidin. RESULTS: Isofraxidin reduced UC symptoms and colonic histopathological impairments. Furthermore, isofraxidin ameliorated the DSS-induced inflammatory response and apoptosis in tissues. S1PR1 was identified as a target of isofraxidin and effectively suppressed activation of the IL-17 signaling pathway. Intriguingly, cellular experiments indicated that overexpression of S1PR1 counteracted the protective effect of isofraxidin. DISCUSSION: In summary, our investigation revealed that isofraxidin could modulate S1PR1 and regulate the IL-17 signaling pathway, thus ameliorating DSS-induced UC. These findings establish a robust foundation for considering isofraxidin as a prospective therapeutic intervention to treat UC.

Ultrasonic treatment maintains the flavor of the melon juice.

Thermal treatment usually leads to the flavor deterioration of melon juice. This study was initiated to evaluate the retention effect of ultrasonic (US) and ultra-high pressure (UHP) on volatile components of melon juice by gas chromatography-mass spectrometer (GC-MS) and gas chromatography-ion mobility spectrometry (GC-IMS). The electronic nose, electronic tongue, and GC-IMS analysis showed that US was much better way to contain the flavor of melon juice than UHP was does. The correlation coefficient between the US and the control was as high as 0.99. The concentration of characteristic aroma components in melon juice after ultrasonic treatment was 2.77 times and 3.02 times higher than that in the control and UHP, respectively. Moreover, the US treatment gave no significant difference in the total soluble solids, pH, and color of the juice. And it dramatically enhanced the flavor profile of melon juice.

Low frequency ultrasound treatment enhances antibrowning effect of ascorbic acid in fresh-cut potato slices.

Ascorbic acid (AsA) is generally used as an antibrowning agent for fresh-cut potato (FCP). However, its browning inhibitory effect is temporary because of its rapid consumption during redox processes. In this study, the effect of browning inhibition in FCP slices was evaluated using low frequency ultrasound (LFU; 40 kHz, 200 W, 3 min) and AsA (0.2%, w/v) treatments alone or in combination. The results showed that LFU combined with AsA (LFU-AsA) treatment could achieve a better antibrowning effect than either treatment alone (higher L*, lower a* and ΔE*), and there was no adverse effect on texture properties. LFU-AsA treatment not only inhibited the activity of PPO more effectively than AsA treatment, but also enhanced the antibrowning effect by retaining higher AsA content. Moreover, it also maintained membrane integrity by limiting lipid peroxidation and solute migration during storage. Overall, LFU-AsA treatment would be a promising method in food preservation industries.

The effect of wheelchair Tai Chi on balance control and quality of life among survivors of spinal cord injuries: A randomized controlled trial.

BACKGROUND: Wheelchair-related falls are common in survivors with spinal cord injury (SCI). We aimed to assess the effects of wheelchair Tai Chi (WCTC) practice on balance control and quality of life (QOL) among SCI survivors. MATERIALS AND METHODS: Forty SCI survivors were equally divided into WCTC and control groups. The control participants only received the normal rehabilitation intervention, while the WCTC intervention involved 30-min sessions, 2 sessions/day, and 5 days/week for 6 weeks. Static sitting balance, trunk muscle strength, handgrip strength, and QOL were evaluated and statistically analyzed. RESULTS: Compared with the control group, static sitting balance, left handgrip strength, and the psychological domain of QOL improved significantly in the WCTC group (time by group interaction, p < 0.05). CONCLUSION: Six weeks' WCTC training improved static sitting balance and QOL in survivors with SCI. It may be a feasible, safe, and effective exercise for SCI survivors.

Discovery of a novel NEDD8 Activating Enzyme Inhibitor with Piperidin-4-amine Scaffold by Structure-Based Virtual Screening.

NEDD8 activating enzyme (NAE) plays an important role in regulating intracellular proteins with key parts in a broad array of cellular functions. Here, we report a structure-based virtual screening of a compound library containing 50 000 small molecular entities against the active site of NAE. Computational docking and scoring followed by biochemical screening and target validation lead to the identification of 1-benzyl-N-(2,4-dichlorophenethyl) piperidin-4-amine (M22) as a selective NAE inhibitor. M22 is reversible for NAE, inhibits multiple cancer cell lines with GI50 values in the low micromolar range, and induces apoptosis in A549 cells. Furthermore, it produces tumor inhibition in AGS xenografts in nude mice and low acute toxicity in a zebrafish model. M22, a novel NAE inhibitor, represents a promising lead structure for the development of new antitumor agents.

Protective Effect of Silibinin on Learning and Memory Impairment in LPS-Treated Rats via ROS-BDNF-TrkB Pathway.

Silibinin, a flavonoid derived from the herb milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1ß and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS-BDNF-TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.

Discovery of 2-azetidinone and 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain as potential cholesterol absorption inhibitors.

Cholesterol absorption inhibitor (CAI) targeting Niemann-Pick C1-like1 protein was developed for the treatment of hyperlipidaemia and only ezetimibe was approved so far. For developing novel CAIs, we synthesized sixteen 2-azetidinone derivatives and thirteen 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain, and their inhibitory activity of cholesterol absorption was evaluated in Caco-2 cell line in vitro. Furthermore, top six compounds were measured by cytotoxicity and partition coefficient, and 2-azetidinone analogue 9e was selected for in vivo study. Finally, 9e considerably reduced total cholesterol, LDL-C, FFA and triglyceride in the serum and increased the rate of HDL-C to total cholesterol, suggesting it could regulate the lipid metabolism and act as a potent CAI.

Simultaneous determination of oridonin, ponicidin and rosmarinic acid from Herba Isodi Rubescentis extract by LC-MS-MS in rat plasma.

An analytical method was developed for the simultaneous quantification of oridonin, ponicidin and rosmarinic acid in rat plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in positive and negative ion modes of operation. Multiple reaction monitoring was used for quantification using the precursor to product ion pairs of m/z 359.100 → 160.9 (rosmarinic acid), m/z 150.1 → 106.9 (acetaminophen as internal standard 1), m/z 365.1 → 347.3 (oridonin), m/z 363.3 → 345.2 (ponicidin) and m/z 258.3 → 201.0 (dextrorphan as internal standard 2). Optimum chromatographic separation was achieved with a BDS Hypersil C18 column (100 × 2.1 mm, 2.4 µm) and a mobile phase consisting of acetonitrile-5mM ammonium acetate containing 0.1% acetic acid (25:75, v/v). The analytes were extracted from rat plasma using a single liquid-liquid extraction technique and the calibration curve was linear within the concentration range of 2-1,000.0 ng/mL for three analytes. The extraction recovery was above 70%, the intra-day and inter-day precision of the quality control (QC) samples was less than 12.45% and the accuracy of the QC samples was 96.99-105.79% of the nominal values. The method was sensitive and reliable and was successfully applied to a pharmacokinetic and bioavailability study of Herba Isodi Rubescentis extract in rats.

[Comparison of 2 µm continuous-wave laser enucleation of the prostate and transurethral resection of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To compare the safety and efficacy of RevoLix 120 W 2 µm continuous-wave (cw) laser enucleation of the prostate with transurethral resection of prostate (TURP) in patients with symptomatic benign prostatic hyperplasia (BPH). And to evaluate clinical value of 120 W 2 µm cw laser enucleation. METHODS: All 168 patients with BPH underwent 2 µm cw laser enucleation (n = 88) or TURP (n = 80) between January 2010 and January 2011. The operative time, drop in hemoglobin, drop in serum sodium, indwelling catheterization time and operative complications were recorded. International prostate symptom score (IPSS), quality of life (QOL), urinary peak flow rate (Qmax) and post-voiding residual urine (PVR) were also compared. RESULTS: The mean operative time was slightly longer in the 2 µm laser group ((63.2 ± 21.6) min) than the TURP group ((59.4 ± 18.6) min) (P > 0.05). Transfusions were not necessary in 2 µm laser group. Catheter indwelling time were (1.8 ± 0.6) days vs. (3.5 ± 2.6) days in 2 µm laser group than in TURP group (t = 3.912, P < 0.05). All cases were followed up for 3 - 12 months, the IPSS, QOL, Qmax and PVR were 6.1 ± 2.0, 4.4 ± 1.6, (18.8 ± 4.8) ml/s and (21.6 ± 16.5) ml in the 2 µm laser group, and were 6.3 ± 2.4, 1.9 ± 1.1, (18.4 ± 4.2) ml/s, (23.2 ± 14.6) ml in TURP group respectively. All the markers were improved significantly compared with that of preoperative in both groups (t = 12.453 - 26.213, P < 0.01), but no statistical differences could be found between the two groups. Perioperative complications were less in the 2 µm laser group. CONCLUSIONS: The 120 W 2 µm cw laser enucleation is an novel excellent treatment for BPH as well as TURP, and has the advantage of significantly less blood loss, shorter hospitalization, shorter catheter indwelling time and rapid recovery after surgery.

[Jinleng method is effective and safe for the treatment of oligospermia and asthenospermia].

OBJECTIVE: The Jinleng method is based on the principle of lowered temperature and diathermic action on the testis. The aim of this study is to investigate the effect and safety of the Jinleng method on oligospermia and asthenospermia. METHODS: We treated 39 infertile males with oligospermia or asthenospermia with Jinleng underpants (Jinleng method) bid for 3 months, observed the changes in the sperm parameters of the patients after the treatment and recorded the pregnancy outcomes of their wives. RESULTS: Of the 36 patients who accomplished the treatment, 31 showed significantly improvement in semen volume, sperm concentration, forward sperm motility, total sperm motility, total sperm count and total motile sperm count (P < 0.05), with an effectiveness rate of 86.1%. Five of the patients wives achieved pregnancy in the 2-month follow-up. Adverse effects were found in none of the patients. CONCLUSION: Jinleng method is effective and safe for the treatment of infertile males with oligospermia and asthenospermia.

[The protection of seed oil of Hippophae rharmnoides on ischemic cerebral infarction in rats].

OBJECTIVE: To study the protection of seed oil of Hippophae rhamnoides on ischemic cerebral infarction in rats and the mechanism of the action. METHOD: Focal cerebral ischemia model was made by middle cerebral artery occlusion(MCAO) in rats. Behavior obstacles of rats were observed. Cerebral infarction volume was determined by Megnetic Resonance Imaging(MRI). RESULT: Seed oil of Hippophae rhamnides 0.7 and 0.35 g.kg-1 could markedly reduce infarction volume after occlusion of middle cerebral artery in rats and also could ameliorate the behavior obstacles of rats. CONCLUSION: These results suggested that seed oil of Hippophae rhamnoides had distinct protection to ischemic cerebral infarction in rats.