a b s t r a c tThe pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.

Previously, we demonstrated that the flavor of milk fermented with Lactobacillus delbrueckii subsp. bulgaricus (IMAU20401) and Streptococcus thermophilus (IMAU40133) at a 1:1000 ratio was superior to that of other ratios of the two strains. In this study, Lactobacillus plantarum P-8 was used as the probiotic bacterium. Six ratios (1:1, 1:5, 1:10, 1:50, 1:100, and 1:1000) of L. plantarum P-8 to yogurt starter were evaluated. A total of 66 volatile compounds including aldehydes, ketones, acids, alcohols, esters, alcohols, and aromatic compounds were identified in milk fermented with the six different L. plantarum P-8 to yogurt starter ratios at 0 d of storage. In particular, key flavor compounds, such as 3-methylbutanal, hexanal, (E)-2-octenal, nonanal, 2-heptanone, 2-nonanone, and acetoin, were identified in the 1:100 ratio treatment. Furthermore, the viable cell count, pH, titratable acidity, viscosity, and syneresis of the milk samples were analyzed during fermentation over 14 d of storage at 4°C. The results indicated that milk can be fermented with L. plantarum P-8 in combination with S. thermophilus and L. delbrueckii subsp. bulgaricus, and the physicochemical characteristics of the milk were not affected by the probiotic bacteria.

No abstract

Rhodomyrtus tomentosa (Aiton) is a flowering plant native to southern and southeastern Asia.Up to date, 106 chemical constituents have been isolated and identified from R. tomentosa. Among these compounds, triterpenoids, flavonoids, phenols and meroterpenoids are the major constituents. Investigations of pharmacological activities of R. tomentosa revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including antibacterial, antitumor, anti-inflammatory and antioxidant activities both in vivo and in vitro. The purpose of this review is to provide an overview of R. tomentosa studies until 2019. This article also intends to review advances in the botanical, phytochemical, pharmacological studies and industrial applications of R. tomentosa, which will provide a useful bibliography for further investigations and applications of R. tomentosa in medicines and foods.

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Lactobacillus delbrueckii subsp. bulgaricus is one of the predominant lactic acid bacterial species used as starter cultures in industrial fermented dairy manufacturing, as it strongly affects the quality of the products. Volatile flavor compound profiles and fermentation characteristics are considered to be the most important indicators for starter culture screening. In the present study, volatile compounds in milk fermented by 17 test strains of L. delbrueckii subsp. bulgaricus and a commercial strain used as a control were identified using solid-phase microextraction (SPME) methods coupled with gas chromatography mass spectrometry (GC-MS). In total, 86 volatile flavor compounds were identified in the fermented milk upon completion of fermentation, including 17 carboxylic acids, 14 aldehydes, 13 ketones, 29 alcohols, 8 esters, and 5 aromatic hydrocarbon compounds. Various volatile flavor compounds (acetaldehyde, 3-methyl-butanal, (E)-2-pentenal, hexanal, (E)-2-octenal, nonanal, 2,3-butanedione, acetoin, 2-heptanone, 2-non-anone, formic acid ethenyl ester) were identified due to their higher odor activity values (>1). In addition, of the 17 test strains of L. delbrueckii subsp. bulgaricus, IMAU20312 (B14) and IMAU62081 (B16) strains exhibited good fermentation characteristics in milk compared with the control strain. The combination of the volatile flavor compound profile and fermentation characteristics in this work could be useful when selecting lactic acid bacteria that may serve as important resources in the development of novel fermented milk products.

Recently, antibody-based therapeutic agents are becoming most leading biologics for treating many diseases, especially for cancer. However, large-scale application of antibody drugs is still hampered by high cost and complex technical process. Endogenous expression of proteins or antibodies can be achieved by applying in vitro transcription (IVT) technique to produce mRNA and then deliver into body, which supplies opportunity to avoid many disadvantages in antibody production as well as clinical applications.Here, we designed the IVT-mRNA encoding the Pembrolizumab, as a commercial anti-PD-1 monoclonal antibody (mAb). The in vitro functional properties and in vivo antitumor activities of the Pembrolizumab expressed from mRNA were both assessed. Maximized expression level of the Pembrolizumab from IVT-mRNA was achieved via optimizing the usage of signal peptide and molar ratio of heavy/light chain. Then the mRNA was further formulated by lipid nanoparticle (LNP), which enable efficient in vivo delivery and protect mRNA from degradation. Intravenously delivered the single dose of mRNA-LNPs in mice resulted in duration of serum Pembrolizumab level over 25 μg/mL more than 35 days. Pharmacokinetic study exhibited significantly enhanced drug exposure of mRNA-encoded mAbs compared with direct injection of Pembrolizumab at same dose. Chronic treatment of the tumor-bearing mice with LNP-encapsulated Pembrolizumab mRNA effectively downregulated the growth of intestinal tumors and improved the animal survival. In brief, our present research demonstrated that the application of LNP-encapsulated IVT-mRNA can change the human body into a protein drug manufacturing site to express full-size mAbs for treating cancer and hold potential to be a novel alternative to protein-based therapies.

Early diagnosis and treatment of colorectal cancer (CRC) significantly improves the survival rate and quality of life. Here we screened for differences in glycoproteins associated with tumor-derived exosomes and validated their clinical value to serve as liquid biopsy biomarkers to diagnosed early CRC. Exosomes were extracted from paracancerous tissues, cancer tissues, and plasma. LC-MS/MS proteomic and glycoproteomics analyses were performed using an LTQ-Orbitrap Elite mass spectrometer. The differences in glycoproteins associated with exosomes of paracancerous tissues and cancer tissue were determined, and their levels in plasma exosomes were determined. Statistical analysis was performed to evaluate the diagnostic efficacy of exosome-associated glycoproteins for CRC. We found that the levels of fibrinogen beta chain (FGB) and beta-2-glycoprotein 1 (β2-GP1) in the exosome of CRC tissue were significantly higher compared with those of paracancerous tissues exosome. The areas under the receiver operating characteristic (ROC) curves of plasma exosomal FGB and β2-GP1 as biomarkers for CRC were 0.871 (95% CI = 0.786–0.914) and 0.834 (95% CI = 0.734–0.901), respectively, compared with those of the concentrations of carcinoembryonic antigen concentration [0.723 (95% CI = 0.679–0.853)] and carbohydrate antigen19-9 concentration [0.614 (95% CI = 0.543–0.715)]. Comprehensive proteomics analyses of plasma exosomal biomarkers in CRC identified biomarkers with significant diagnostic efficacy for early CRC, which can be measured using relatively non-invasive techniques.