Sono-activated materials for enhancing focused ultrasound ablation: Design and application in biomedicine.

The ablation effect of focused ultrasound (FUS) has played an increasingly important role in the biomedical field over the past decades, and its non-invasive features have great advantages, especially for clinical diseases where surgical treatment is not available or appropriate. Recently, rapid advances in the adjustable morphology, enzyme-mimetic activity, and biostability of sono-activated materials have significantly promoted the medical application of FUS ablation. However, a systematic review of sono-activated materials based on FUS ablation is not yet available. This progress review focuses on the recent design, fundamental principles, and applications of sono-activated materials in the FUS ablation biomedical field. First, the different ablation mechanisms and the key factors affecting ablation are carefully determined. Then, the design of sono-activated materials with high FUS ablation efficiencies is comprehensively discussed. Subsequently, the representative biological applications are summarized in detail. Finally, the primary challenges and future perspectives are also outlined. We believe this timely review will provide key information and insights for further exploration of focused ultrasound ablation and new inspiration for designing future sono-activated materials. STATEMENT OF SIGNIFICANCE: The ablation effect of focused ultrasound (FUS) has played an increasingly important role in the biomedical field over the past decades. However, there are also some challenges of FUS ablation, such as skin burns, tumour recurrence after thermal ablation, and difficulty in controlling cavitation ablation. The rapid advance in adjustable morphology, enzyme-mimetic activity, and biostability of sono-activated materials has significantly promoted the medical application of FUS ablation. However, the systematic review of sono-activated materials based on FUS ablation is not yet available. This progress review focuses on the recent design, fundamental principles, and applications in the FUS ablation biomedical field of sono-activated materials. We believe this timely review will provide key information and insights for further exploration of FUS ablation.

Active compounds and potential targets of Shuganning injection in the treatment of hepatocellular carcinoma by network pharmacology and in vitro validation.

Shuganning injection (SGNI), a TCM (traditional Chinese medicine) injection with good hepatoprotective effects, exerted therapeutic effects on hepatocellular carcinoma (HCC). However, the active compounds and effects of SGNI on HCC remain unclear. The objective of this study was to investigate the active compounds and potential targets of SGNI in the treatment of HCC, and explore the molecular mechanisms of main compounds. Network pharmacology was applied to predict the active compounds and targets of SGNI on cancer. The interactions between active compounds and target proteins were validated by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and pull-down assay. The in vitro test of the effects and mechanism of vanillin and baicalein was elucidated by MTT, western blot, immunofluorescence, and apoptosis analysis. According to compound characteristics, targets, etc., two typical active ingredients (vanillin and baicalein) were selected as representatives to explore the effects on HCC. Vanillin (an important food additive) bound to NF-κB1 and baicalein (a bioactive flavonoid) bound to FLT3 (FMS-like tyrosine kinase 3) were confirmed in this study. Vanillin and baicalein both inhibited cell viability and promoted apoptosis of Hep3B and Huh7 cells. In addition, both vanillin and baicalein could enhance the activation of the p38/MAPK (mitogen-activated protein kinase) signaling pathway, which may partially explain the anti-apoptosis effects of the two compounds. In conclusion, two active compounds of SGNI, vanillin and baicalein, promoted apoptosis of HCC cells via binding with NF-κB1 or FLT3, and regulating the p38/MAPK pathway. Baicalein and vanillin may be good candidates for HCC treatment on drug development.

Stachydrine hydrochloride inhibits hepatocellular carcinoma progression via LIF/AMPK axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is not only one of the four highest malignancies, but also the principal reason of cancer-related death worldwide, yet no effective medication for anti-HCC is available. Stachydrine hydrochloride (SH), an alkaloid component in Panzeria alaschanica Kupr, exhibits potent antitumor activity in breast cancer. However, the anti-HCC effects of SH remain unknown. PURPOSE: Our study assessed the therapeutic effect of SH on HCC and tried to clarify the mechanisms by which it ameliorates HCC. No studies involving using SH for anti-HCC activity and molecular mechanism have been reported yet. STUDY DESIGN/METHODS: We examined the cell viability of SH on HCC cells by MTT assay. The effect of SH on cell autophagy in HCC cells was verified by Western blot and Immunofluorescence test. Flow cytometry was performed to assess cell-cycle arrest effects. Cell senescence was detected using ß-Gal staining and Western blot, respectively. An inhibitor or siRNA of autophagy, i.e., CQ and si LC-3B, were applied to confirm the role of autophagy acted in the anti-cancer function of SH. Protein expression in signaling pathways was detected by Western blot. Besides, molecular docking combined with cellular thermal shift assay (CETSA) was used for analysis. Patient-derived xenograft (PDX) model were built to explore the inhibitory effect of SH in HCC in vivo. RESULTS: In vitro studies showed that SH possessed an anti-HCC effect by inducing autophagy, cell-cycle arrest and promoting cell senescence. Specifically, SH induced autophagy with p62 and LC-3B expression. Flow cytometry analysis revealed that SH caused an obvious cell-cycle arrest, accompanied by the decrease and increase in Cyclin D1 and p27 levels, respectively. Additionally, SH induced cell senescence with the induction of p21 in HCC cell lines. Mechanistically, SH treatment down-regulated the LIF and up-regulated p-AMPK. Moreover, PDX model in NSG mice was conducted to support the results in vitro. CONCLUSION: This study is the first to report the inhibitory function of SH in HCC, which may be due to the induction of autophagy and senescence. This study provides novel insights into the anti-HCC efficacy of SH and it might be a potential lead compound for further development of drug candidates for HCC.

Arsenic(iii) removal from aqueous solution using TiO2-loaded biochar prepared by waste Chinese traditional medicine dregs.

Oxidation of As(iii) to As(v) is an effective way to improve the performance of most arsenic removal technologies. In this study, a new alternative biosorbent, TiO2-loaded biochar prepared by waste Chinese traditional medicine dregs (TBC) was applied in remediation for As(iii) from aqueous solution. Compared with unmodified biochar, the specific surface areas and total pore volumes of TBC increased while the average aperture decreased due to the loading of nano-TiO2. The X-ray diffraction (XRD) of TBC confirmed that the precipitated titanium oxide was primarily anatase. pH did not have a significant effect on the adsorption capacity at 10 mg L-1 As(iii) in suspension with a pH ranging from 2 to 10. Adsorption kinetics data were best fitted by the pseudo-second-order model (R 2 > 0.999). The Sips maximum adsorption capacity was 58.456 mg g-1 at 25 °C, which is comparable with other adsorbents reported in previous literature. The Gibbs free energy (ΔG) of As(iii) adsorption was negative, indicating the spontaneous nature of adsorption. The results of free radical scavenging and N2 purging experiments indicated that O2 acted as an electron accepter and O2˙- dominated the oxidation of As(iii). The oxidation of As(iii) obviously affected the adsorption capacity for As(iii) by TBC. X-ray photoelectron spectroscopy (XPS) studies showed that As(iii) and As(v) existed on the surface of TBC, suggesting that the oxidation of As(iii) occurred. TBC played multiple roles for As(iii), including direct adsorption and photocatalytic oxidation adsorption. Regeneration and stability experiments showed that TBC was an environment-friendly and efficient adsorbent for As(iii) removal.

The Influence of Standardized Residency Training on Trainees' Willingness to Become a Doctor: A Comparison between Traditional Chinese Medicine and Western Medicine.

A standardized residency training program (SRT) was launched in Shanghai in 2010, for both Western Medicine (WM) and Traditional Chinese Medicine (TCM). This study aimed to assess whether the program impacted trainees' willingness to become a doctor and whether the program had different effects among WM and TCM trainees. A structured questionnaire was distributed to 2114 trainees to assess their perceptions and satisfaction with the program and their willingness to become a doctor after the exposure to the program. The trainees' characteristics were compared between WM and TCM specialties using X2 tests. The potential factors associated with trainees' perception of the program and willingness to become a doctor after the exposure to the SRT program were assessed by multiple linear and logistic regression models. Compared to WM trainees (n = 1853), TCM trainees (n = 261) would be more likely to become doctors if there were no SRT program (p = 0.003). Both individual and program-wide (different specialties) factors contributed to trainees' perception, overall satisfaction, and willingness. Only specialty played an independent role in the associations with all three outcome variables. Inequality of characteristics between TCM and WM trainees reduced TCM trainees' willingness to become a doctor after the exposure to the SRT program.

Mindfulness and asthma symptoms: A study among college students.

INTRODUCTION: Given the known link between asthma and stress as well as the link between mindfulness and stress, we explore the possible association between trait mindfulness and asthma-related diagnosis and symptoms with a cross-sectional study. METHOD: In 2014, we surveyed a sample of college students in their freshman year, from a public university in Shanghai, China. We used three multilevel logistic regressions to estimate the association between trait mindfulness (measured by Mindful Awareness Attention Scale, MAAS) and self-report of ever having an asthma diagnosis, ever having had persistent dry cough, and ever having had wheezing symptoms. Age, gender, household registration status, and the frequency of smog in the respondent's hometown were used as control variables in the study. The home province of the student was used as the cluster variable in the multilevel models. RESULTS: Among the 1392 students in the analysis sample (mean age = 18.3), 47 (3.4%) self-reported an asthma diagnosis, 251 (18.1%) reported having had persistent dry cough, and 100 (7.2%) reported having had wheezing symptoms. A one-unit increase in MAAS is negatively associated with having a self-reported asthma diagnosis (Odds Ratio (OR): 0.662, 95% Confidence Interval (CI): 0.452, 0.969, p = 0.034), having had persistent dry cough (OR: 0.658, 95% CI: 0.545, 0.795, p < 0.001), and wheezing (OR = 0.747, 95% CI: 0.569, 0.981, p = 0.036). DISCUSSION: This is the first study to suggest a link between trait mindfulness and asthma. Our finding provides evidence that people with higher level of mindfulness are less likely to have had an asthma diagnosis and less likely to have the symptoms of persistent dry cough and wheezing.

Synthesis of acyl oleanolic acid-uracil conjugates and their anti-tumor activity.

BACKGROUND: Oleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies. RESULTS: Five acyl oleanolic acid-uracil conjugates were synthesized. Most of the IC50 values of these conjugates were lower than 10.0 µM, and some of them were even under 0.1 µM. Cytotoxicity selectivity detection revealed that conjugate 4c exhibited low cytotoxicity towards the normal human liver cell line HL-7702. Further studies revealed that 4c clearly possessed apoptosis inducing effects, could arrest the Hep-G2 cell line in the G1 phase, induce late-stage apoptosis, and activate effector caspase-3/9 to trigger apoptosis. CONCLUSIONS: Conjugates of five different acyl OA derivatives with uracil were synthesized and identified as possessing high selectivity toward tumor cell lines. These conjugates could induce apoptosis in Hep-G2 cells by triggering caspase-3/9 activity.Graphical abstractFive acyl oleanolic aicd-uracil conjugates were synthesized. These conjugates exhibited selective cytotoxicity toward tumor cells achieved via inducing apoptosis by activation of caspase-3/9.

The effectiveness of mindfulness-based stress reduction (MBSR) for survivors of breast cancer: study protocol for a randomized controlled trial.

BACKGROUND: After treatment completion, breast cancer (BC) survivors frequently experience residual symptoms of pain, fatigue, high levels of psychological stress, anxiety, depression, fear of recurrence, and metastasis. Post-treatment stress, in particular, can adversely affect health-related quality of life, which, in turn, induces onset or recurrence of chronic diseases. Effective interventions that target these psychological symptoms and their physiological consequences are needed, especially for economically disadvantaged patients. However, in China, few evidence-based intervention strategies have been established among BC survivors. This study will formally adapt, develop, and evaluate an intensive mindfulness-based stress reduction (MBSR) intervention protocol to improve mental health, quality of life, and compliance with medication among Chinese BC survivors. METHODS: A randomized, waitlist-controlled clinical trial will be conducted. Based on our power calculation, 418 BC survivors will be recruited from 10 low-income communities in Shanghai. All subjects will be randomly assigned either to the MBSR program or to a waitlisted usual care regimen that will offer the MBSR program after the completion of the other trial arm (after 6 months follow-up). Our 8-week MBSR intervention program will provide systematic training to promote stress reduction by self-regulating arousal to stress. Assessments will be made at baseline, 4 weeks (in the middle of the first MBSR intervention), 8 weeks (at the end of the first MBSR intervention), 6 months, and 12 months, and will include measures of psychological symptoms (depression, anxiety, and perceived stress), quality of life, and medication adherence. The expected outcome will be the improvement in psychological symptoms, quality of life, and medication compliance in the MBSR intervention group. DISCUSSION: This study will help develop an affordable, self-care psychological intervention protocol to help Chinese BC survivors improve their quality of life, and could be helpful in further developing affordable disease management plans for patients of other chronic diseases. TRIAL REGISTRATION: ChiCTR-IOR-14005390 (10/27/2014).