A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells. / æ–°åž‹è¡¥éª¨è„‚é šæ°¨åŸºèƒè¡ç”Ÿç‰©è¯±å¯¼äººä¸‰é˜´æ€§ä¹³è ºç™Œç»†èƒžå‡‹äº¡.

OBJECTIVES: To synthesize new bakuchiol aminoguanidine derivatives and test their effect on viability and apoptosis of human triple-negative breast cancer (TNBC) cells. METHODS: Two bakuchiol derivatives 1 and 2 were obtained by formylation and Shiff base reaction of bakuchol. The structures of derivatives 1 and 2 were identified by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analysis. Human TNBC MDA-MB-231 cells were treated with bakuchiol and its derivatives and cell viability was measured by MTT assay. Apoptosis was detected by fluorescence microscopy and flow cytometry with Annexin V-FITC/PI staining. The expressions of apoptosis-related proteins were analyzed with Western blotting. The JC-1 and reactive oxygen species (ROS) assay kits were used to determine the effect of new bakuchiol derivatives on mitochondrial function. RESULTS: Based on spectroscopic analysis, a new bakuchiol schiff base derivative was elucidated as 2-{(E)-5-[(S, E)-3, 7-dimethyl-3-vinylocta-1, 6-dien-1-yl]-2-hydroxylbenzylidene} hydrazine-1-carboximidamide (derivative 2). Bakuchiol and its derivatives 1 and 2 all showed cytotoxic activity against the MDA-MB-231 cells. Derivative 2 exhibited the most potent cytotoxic activity to MDA-MB-231 cell with IC50 of (13.11±1.09), (6.91±1.78), and (2.23±1.32) µmol/L after 24, 48, and 72 h. It had low toxicity to normal mouse liver (AML-12) cells with IC50 of (31.23±1.58) µmol/L at 72 h. Fluorescence microscopy and flow cytometry demonstrated apoptosis in breast cancer cells after treating with derivative 2 in a concentration dependent manner. Western blotting showed that after derivative 2 treatment, the expression of apoptosis-related proteins cytochrome C, cleaving caspase-3 and Bax/Bcl-2 radio in MDA-MB-231 cells increased; in addition, apoptosis was associated with the decreased mitochondrial membrane potential and increased reactive oxygen species accumulation. CONCLUSIONS: The novel bakuchiol aminoguanidine derivative (derivative 2) is capable of inducing apoptosis in MDA-MB-231 cells, but has low toxicity to normal liver cells, suggesting that it may be used as a lead compound for an anti-TNBC agent.

Assessing the impact of ultra-thin diamond nanothreads on the glass transition temperature of a bituminous binder.

Low-temperature cracking and rutting are the most destructive problems of bitumen that hinder the application of high-performance bitumen engineering, which is dependent on its glass transition temperature (Tg). Through in silico studies, this work has systematically investigated the Tg of a bituminous binder with the addition of diamond nanothread (DNT) fillers with varying filler content, alignment, distribution, and functional groups. In general, the glass transition phenomenon of the bitumen is determined by the mobility of its constituent molecules. Tg is found to increase gradually with the increase in the weight percentage of DNT and then decreases when the weight percentage exceeds 5.05 wt%. The enhancement effect on Tg is weakened when DNTs are distributed vertically or functionalized with functional groups. Specifically, DNT fillers induce inhomogeneity, which promotes the motion of small molecules while hindering the motion of large molecules. The aggregation of DNTs and the molecular environment in the vicinity of DNTs directly affect Tg. In summary, aggregation and adhesion are the dominant mechanisms affecting the mobility of the constituent molecules in the DNT/bitumen system and thus its glass transition temperature. This work provides in-depth insights into the underlying mechanisms for the glass transition of a bituminous binder, which could serve as theoretical guidance for tuning the low-temperature performance of the bituminous binder.

Comparative study of three cultivars of jaboticaba berry: nutrient, antioxidant and volatile compounds.

Jaboticaba is a tropical plant and its fruit rich in nutrients, volatile compounds, and biological activities, which considered to be an edible health benefits plant. Despite its popularity for fresh consumption, jaboticaba is rarely used in intensive processing in China. The content of nutrients and antioxidant in jaboticaba greatly impacts how it is processed healthy food. In this study, we evaluated the nutrients, antioxidant capacity, and volatile compounds of three jaboticaba cultivars including Sabara, Argentina, and Fukuoka, respectively. Our results revealed each variety has its merits. Sabara had an abundance of volatile compounds, a suitable acid-sugar ratio, and a slightly lower antioxidant capacity, making it suitable for fresh consumption. Argentina is the richest in volatile compounds in ripe fruit, but slightly lighter in taste and acid-sugar ratio, making it suitable for dry products. The large size, juicy flesh, low acid-sugar ratio, and less volatile compounds content of Fukuoka also make it suitable for juice processing. Three cultivars of jaboticaba berry exhibited different characteristics, providing reference evidence for the manufacturing and processing of jaboticaba health food.

UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) is a new type of gene delivery technology. MiR-21-5p was highly expressed in a variety of cancers. In this paper, miR-21-5p inhibitor was transfected into lung cancer cells by UTMD to observe its role in lung cancer. METHODS: StarBase was used to analyze the miR-21-5p expression in lung cancer patients and its relationship with the prognosis of the patients. MiR-21-5p expression in lung cancer tissues or cell lines was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Effects of gradient concentration (0, 5, 10, 20, 30%) of SonoVue or gradient mechanical index (MI) (0, 0.5, 1, 1.5, 2 W/cm2) on the cell viability were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The targeting relationship between miR-21-5p and B-cell translocation gene 2 (BTG2) was predicted by TargetScan and confirmed by dual-luciferase reporter assay, while the expressions of the two genes were determined by qRT-PCR. Through liposome transfection or UTMD transfection, the effects of miR-21-5p/BTG2 on the biological behaviors of lung cancer cells, the size of xenograft tumors and the expressions of ki67 and miR-21-5p were measured by qRT-PCR, western blot, cell function experiments and immunohistochemistry, respectively. RESULTS: MiR-21-5p expression was upregulated in lung cancer, which was associated with a poor prognosis. The optimal ultrasound conditions were 10% SonoVue concentration and 1 W/cm2. UTMD transfection exerted a stronger effect than liposome transfection. MiR-21-5p promoted cell viability, proliferation and migration yet suppressed apoptosis by targeting BTG2. MiR-21-5p inhibitor reduced the size and volume of xenograft tumor and the expressions of ki67 and miR-21-5p in xenograft tumor tissues. CONCLUSION: UTMD-mediated miR-21-5p inhibitor can more effectively suppress the development of lung cancer.

[Clinical features of patients with venous thromboembolism: 177 case analysis in 10 years].

OBJECTIVE: To analyze the clinical characteristics and risk factors of patients with confirmed venous thromboembolism (VTE) in order to improve recognition of VTE, and reduce the rate of missed diagnosis and wrong diagnosis. METHODS: A retrospectively review was performed for 205 patients diagnosed with VTE confirmed by CT pulmonary angiography (CTPA), radionuclide pulmonary ventilation/perfusion (V/Q) imaging, lower extremity deep vein ultrasound or venography in the First Affiliated Hospital of Bengbu Medical College from January 2009 to December 2018. The clinical manifestations, laboratory examination results, imaging results, treatment and prognosis of patients diagnosed with VTE were analyzed. The clinical possibility was assessed by pulmonary thromboembolism (PTE) simplified Wells score and deep venous thrombosis (DVT) Wells score. 130 non-VTE patients admitted in the same period were enrolled as controls, and the risk factors of VTE were screened by multivariate Logistic regression analysis. RESULTS: Among 205 VTE patients, 14 cases had incomplete data, 2 cases were complicated with other diseases deteriorated, 2 cases were excluded because of economic reasons, 10 cases abandoned treatment because of serious illness, and finally 177 cases were included in the analysis. The main clinical symptoms of VTE patients were chest tightness (36.16%), followed by chest pain (29.94%), dyspnea (29.38%) and hemoptysis (24.29%). Swelling or tenderness of unilateral/bilateral lower extremities (38.98%) and lung moist rale (20.90%) were the most common signs. ST-T changes were the main changes in electrocardiogram (ECG, 49.15%), followed by SIQIIITIII or QIIITIII changes (35.03%). Only 5.65% of the patients had plasma D-dimer less than 0.5 mg/L. 31.07% (55/177) patients had normal arterial blood gas results. Of the 177 VTE patients, 175 were diagnosed as PTE by CTPA, with bilateral/multi-lobar pulmonary artery embolism and its branches being the main type [44.57% (78/175)]. Two cases were diagnosed as PTE by V/Q imaging. Among them, 112 cases were received lower extremity deep venous ultrasound or lower extremity deep venography, 51 cases were diagnosed as lower extremity DVT, with thrombosis of popliteal and above vein as common [68.63% (35/51)]. The clinical possibility assessment showed that 67.23% (119/177) patients might have PTE (PTE simplified Wells score greater than or equal to 2), 38.98% (69/177) patients might have lower extremity DVT (DVT Wells score greater than or equal to 2). Multivariate Logistic regression analysis showed that operation less than 4 weeks [odds ratio (OR) = 5.503, 95% confidence interval (95%CI) = 1.577-19.206, P = 0.007], trauma or fracture less than 3 months (OR = 6.771, 95%CI = 1.510-30.370, P = 0.012), VTE history (OR = 0.072, 95%CI = 0.009-0.549, P = 0.011) were independent risk factors for VTE occurrence. Thrombolytic therapy was administered in 13 cases while anticoagulant therapy alone was prescribed in 164 cases. 176 patients recovered, while 1 case died. CONCLUSIONS: VTE clinical manifestations are not specific. Patients with risk factors should be vigilant, be strengthen with diagnostic awareness, paid attention to the evaluation of clinical possibilities. Timely thrombolytic or anticoagulant treatment after diagnosis, can improve the survival rate.