New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

Peroxiredoxin 1 regulates crosstalk between pyroptosis and autophagy in oral squamous cell carcinoma leading to a potential pro-survival.

Peroxiredoxin 1 (Prdx1), a vital antioxidant enzyme, has been proven to play an important role in the occurrence and development of cancers, but its effects on oral squamous cell carcinoma (OSCC) remain unclear. Here, we performed bioinformatics analysis and immunohistochemical (IHC) staining to confirm that Prdx1 was higher in OSCC tissues than in normal tissues. Consistently, RT-PCR and Western blot showed elevated Prdx1 expression in OSCC cell lines compared to human oral keratinocytes (HOK), which could be knockdown by small interfering RNA (siRNA) and Lentiviral vector delivery of short hairpin RNA (shRNA). Prdx1 silencing significantly blocked OSCC cell proliferation and metastasis, as evidenced by the CCK8, colony formation, in vivo tumorigenesis experiment, wound healing, transwell assays, and changes in migration-related factors. siPrdx1 transfection increased intracellular reactive oxygen species (ROS) levels and provoked pyroptosis, proved by the upregulation of pyroptotic factors and LDH release. Prdx1 silencing ROS-independently blocked autophagy. Mature autophagosome failed to form in the siPrdx1 group. Up-regulated autophagy limited pyroptosis triggered by Prdx1 deficiency, and down-regulated pyroptosis partly reversed siPrdx1-induced autophagy defect. Collectively, Prdx1 regulated pyroptosis in a ROS-dependent way and modulated autophagy in a ROS-independent way, involving the crosstalk between pyroptosis and autophagy.

Mindfulness and negative emotions among Chinese college students: chain mediation effect of rumination and resilience.

Objective: This study examines the mediation effect of rumination and resilience between the relationship of mindfulness and negative emotions in Chinese college students. Method: A total of 3,038 college students (19.94 ± 1.10) were investigated by Mindfulness Attention Awareness Scale (MASS), Rumination Response Style Scale (RRS), Resilience Scale (RES) and Depression-anxiety-pressure scale (DASS-21), and the mediation analyses were conducted by adopting PROCESS macro in the SPSS software. Results: ① Mindfulness was negatively associated with rumination and negative emotions (r = -0.69, -0.72; P < 0.01), and positively associated with resilience (r = 0.63, P < 0.01). Rumination was negatively associated with resilience (r = -0.59, P < 0.01), and positively associated with negative emotions (r = 0.83, P < 0.01). Resilience was negatively associated with negative emotions (r = -0.71, P < 0.01). ② Mindfulness can not only directly predict negative emotions (95%CI, -0.12~-0.09) but also affects negative emotions through three indirect paths: Rumination was a mediator (95%CI, -0.24~-0.20), resilience was a mediator (95%CI, -0.07~-0.06), and resilience and rumination were a chain mediator (95%CI, -0.04 ~ -0.03). Conclusion: Mindfulness not only influences negative emotions directly, but also through the mediating effect of rumination and resilience indirectly.

The circadian clock has roles in mesenchymal stem cell fate decision.

The circadian clock refers to the intrinsic biological rhythms of physiological functions and behaviours. It synergises with the solar cycle and has profound effects on normal metabolism and organismal fitness. Recent studies have suggested that the circadian clock exerts great influence on the differentiation of stem cells. Here, we focus on the close relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system. The underlying mechanisms include hormone signals and the activation and repression of different transcription factors under circadian regulation. Additionally, the clock interacts with epigenetic modifiers and non-coding RNAs and is even involved in chromatin remodelling. Although the specificity and safety of circadian therapy need to be further studied, the circadian regulation of stem cells can be regarded as a promising candidate for health improvement and disease prevention.

Perfusion of a cerebral protective solution enhances neuroprotection in a rabbit model of occlusion-reperfusion: prolonged cerebral dormancy time.

In the present study, we investigated the effect of a cerebral protective solution on prolongation of cerebral dormancy time in a rabbit model of occlusion-reperfusion. In a control group, rabbits were anesthetized and the four cerebral arteries (the left and right common carotid arteries and vertebral arteries) were occluded for 7.5 min followed by reperfusion. All six rabbits in the control group died. In contrast, a second group underwent perfusion of a cerebral protective solution for 15 min between artery occlusion and reperfusion. All six rabbits in this group survived. However, when the perfusion solution was changed to 5% glucose solution or rabbit plasma in two other groups, the rabbits in both the latter two groups also died. Neuroprotection was also observed when the protective solution was administered for 30-60 min after the onset of artery occlusion and before the return of blood flow (reperfusion). To understand the high rate of thrombotic stroke in the clinic, we assessed the influence of different organ tissue infusions on blood coagulation in vitro and found that blood clotting occurred faster in the presence of brain tissue infusion compared to liver, kidney, and heart tissue infusions. These results indicate a higher rate of thrombosis in brain tissue compared to any of the other tissues tested. The current study shows that perfusion of a cerebral protective solution produced a significant neuroprotective benefit in our rabbit model of occlusion-reperfusion, suggesting that administration of a cerebral protective solution may be an effective approach for the treatment of ischemic stroke.