Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

Synthesis and antifungal activity of 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6-olide.

The racemic 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6-olide, the analog of natural product (6R)-3,7-dimethyl-7-hydroxy-2-octen-1,6-olide, was totally synthesized using easily available (E)-2-(2-carboxyvinyl)benzoic acid as a raw material in nine-step reactions including three key steps of Wittig reaction, epoxidation, and cyclization, with an overall yield of 10.3%. The bioassay results showed that ( ± )-2 exhibited stronger antifungal activity than the natural product ( ± )-1 and (R)-1 against Alternaria solani with an EC50 value of 27.36 µg/ml.

Total synthesis of 3,7-dimethyl-7-hydroxy-2-octen-1,6-olide and 3,7-dimethyl-2,6-octadien-1,6-olide.

3,7-Dimethyl-7-hydroxy-2-octen-1,6-olide and 3,7-dimethyl-2,6-octadien-1,6-olide, the natural bioactive compounds isolated from the fruit of Litsea cubeba and the liverwort Plagiochila rutilans, were totally synthesized using easily available cis-geraniol as raw material in short, convenient, and low-cost, five-step reactions including three steps of oxidation, cyclization, and dehydration, with an overall yield of 47.5% and 37.3%.

Insights into graphene oxide/ferrihydrite adsorption as pretreatment during ultrafiltration: Membrane fouling mitigation and disinfection by-product control.

In this study, a novel adsorbent of graphene oxide (GO) incorporated ferrihydrite (FH) was fabricated and integrated with ultrafiltration (UF) to remove natural organic matter (NOM), the crucial cause of membrane fouling and major precursor of disinfection by-products (DBPs). Compared with FH and powdered activated carbon (PAC), GO/FH exhibited superior removal for high molecular weight (HMW) humic- and fulvic-like substances and low molecular weight (LMW) protein. The cake layer formed by GO/FH alleviated the deposition of NOM on membrane surface or inside membrane pores. Therefore, GO/FH reduced 89% and 95% total fouling resistance and irreversible membrane resistance, respectively, together with the lowest increment of transmembrane pressure. Pearson correlation analysis indicated that DOC, rather than specific ultraviolet absorbance (SUVA) and UV254, was significantly correlated to the formation of trihalomethanes (THMs) and haloacetic acids (HAAs) when SUVA was below 4 L/mg-C.m. Whilst the HMW NOM (1-20 kDa) was highly related to dibromochloromethane (DBCM) (r = 0.98-1), the LMW fraction (< 1 kDa) was correlated with dibromochloromethane (TCAA) and dichloroacetic acid (DCAA) (r = 0.88-0.98). Inspiringly, GO/FH-UF reduced 90% of carbonaceous DBPs, the concentrations of which well met the WHO Guidelines. In summary, GO/FH-UF substantially alleviated membrane fouling and dramatically reduced DBP formation potential.

The fungicidal terpenoids and essential oil from Litsea cubeba in Tibet.

A new C9 monoterpenoid acid (litseacubebic acid, 1) and a known monoterpene lactone (6R)-3,7-dimethyl-7-hydroxy-2-octen-6-olide (2), along with three known compounds--vanillic acid (3), trans-3,4,5-trimethoxylcinnamyl alcohol (4), and oxonantenine (5)--were isolated with bioassay-guided purification from the fruit extract of Litsea cubeba collected in Tibet. The structure of 1 was elucidated by MS, ¹H-NMR, ¹³C-NMR, COSY, HSQC, HMBC, NOE spectral data as 2,6-dimethyl-6-hydroxy-2E,4E-hepta-2,4-diene acid. Additionally 33 compounds were identified from the essential oil of L. cubeba. The preliminary bioassay results showed that 1 and 2 have good fungicidal activities against Sclerotinia sclerotiorum, Thanatephorus cucumeris, Pseudocer-cospora musae and Colletotrichum gloeosporioides at the concentration of 588 and 272 µM, and the essential oil has good fungicidal activities against T. cucumeris and S. sclerotiorum, with IC50 values of 115.58 and 151.25 µg/mL, repectively.

MiR-491-3p is down-regulated in postmenopausal osteoporosis and affects growth, differentiation and apoptosis of hFOB1.19 cells through targeting CTSS.

BACKGROUND: Postmenopausal osteoporosis (PMO) is a common disease related to aging, which has been paid increasing attention in recent years because of its serious complications. MiR-491-3p was found to play a crucial roles in several diseases. However, the role of miR-491-3p in PMO has yet not been studied. Our research intends to explore the impact of miR-491-3p on PMO in the in vitro model. MATERIAL AND METHODS: The expression patterns of miR-491-3p and cathepsin S (CTSS) in patients with PMO were acquired from the GEO database. The human osteoblast cell hFOB1.19 was used to detect the function of miR-491-3p and CTSS in PMO. The viability and apoptosis of hFOB1.19 cells were measured by cell counting kit 8 and flow cytometry assays. The apoptosis and differentiation related proteins were analyzed by western blotting. The relationship between miR-491-3p and CTSS was predicted by appropriate software and affirmed by luciferase assay. RESULTS: MiR-491-3p expression was lower in patients with PMO. The up-regulation of miR-491-3p in hFOB1.19 cells increased their viability and differentiation and inhibited their apoptosis. CTSS, which was highly expressed in patients with PMO, was confirmed as a direct target of miR-491-3p and was found to be inversely modulated by miR-491-3p. The rescue assays showed that overexpression of CTSS suppressed the promoting effects of miR-491-3p mimic on the proliferation and differentiation of hFOB1.19 cells, and repressed the inhibitory effects of miR-491-3p mimic on apoptosis of hFOB1.19 cells. CONCLUSIONS: The results of our study showed that miR-491-3p could ameliorate biological characteristics of hFOB1.19 cells by reducing CTSS expression suggesting that miR-491-3p/CTSS might be a potential biomarker for the diagnosis and treatment of PMO.