Latest ArticlesUDP-glucose: flavonoid 3-O-glucosyltransferase (UF3GT) uses flavones, dihydroflavonol or anthocyanin as the acceptor and uridine 5′-diphosphate-sugar as the donor to catalyze the production of flavonoid 3-O-glycoside compounds. Based on sequence homology and transcriptome data, we screened and cloned a UF3GT gene named CtUF3GT (GenBank No. OM948976) from safflower. Biological information analysis demonstrate that CtUF3GT has highly conserved PSPG motif. The open reading frame of CtUF3GT is 1 446 bp, encoding 481 amino acids, with a presumed molecular weight of 52.36 kD and a theoretical isoelectric point of 5.33. Multiple sequence alignment indicate that CtUF3GT has a high homology with UF3GT from Asteraceae, and phylogenetic analysis showed that CtUF3GT clusters with functional identified UF3GTs from other species. The purified recombinant protein glucosylated kaempferol and quercetin to biosynthesis of kaempferol 3-O-glucoside and quercetin 3-O-glucoside, respectively. And CtUF3GT prefered to use kaempferol as substrate. qRT-PCR analysis showed that the UF3GT gene was most highly expressed in flowers, followed by leaves, with very low expression in bracts and stems, and no expression in roots. The expression of UF3GT gene showed a trend of increasing and then decreasing at different stages of flower development. The expression of CtUF3GT gene in safflower with different flower color was highly significant (P < 0.01) at S1, S2, S5, S6 and S7 stages of flower development, in which the expression of CtUF3GT in white safflower was 5.3 and 3.1 times higher than that in red safflower at S6 and S7 stages. This study lays the foundation for further exploring the role of CtUF3GT in the mechanism of safflower flavonoid secondary metabolite biosynthesis and accumulation.
Tumor vaccine is one of the most promising therapeutic strategies in tumor immunotherapy. It promotes the antigen presentation process by delivering tumor antigen and then activates the anti-tumor immune response. As a new class of vaccines, messenger RNA (mRNA) vaccines can activate the immune system to achieve the purpose of immunotherapy by delivering the mRNA sequence of a specific antigen into the body and expressing the corresponding antigen protein. Compared with traditional vaccines, mRNA vaccines have the advantages of a short production cycle, high effectiveness, and strong immunogenicity. In recent years, the application of mRNA vaccines in tumor immunotherapy has attracted widespread attention, but the instability and low delivery efficiency of mRNA limit its application. Nano delivery system can effectively solve the problem of mRNA vaccine delivery, greatly promote the research process and clinical application of mRNA tumor vaccines, and has become a hot spot in the research of mRNA vaccines. In this review, we introduced the mRNA tumor vaccines, focusing on the application of nano delivery system in mRNA tumor vaccines, in order to provide new ideas and new methods for the efficient delivery of mRNA tumor vaccines and tumor immunotherapy.
Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel, located on cell membranes. TRPV3 is extensively expressed in various organs such as skin, brain, dorsal root ganglia, heart and colon. It's reported that TRPV3 involves in many physiological processes including sensation, skin barrier formation, hair growth and vasodilatation, and pathological processes like pruritus, cutaneous inflammatory disease and cancer. TRPV3 can respond to innoxious warm stimulation (≥ 33 ℃), endogenous substances (e.g., farnesylpyrophosphate) and exogenous small molecules (e.g., carvacrol, camphor and 2-APB). Recently, several natural or synthetic small molecules (e.g., osthole, 74a and dyclonine) have been shown to suppress TRPV3 activity, accompanying with therapeutic efficacy in animal models of diseases, which suggests the potential of TRPV3 as drug target. This paper reviews the research progress on the structure, physiological functions, related diseases and modulators of the TRPV3 channel to provide theoretical references for the future study on TRPV3 channel.
Ten compounds were isolated from the water extract of Eriocaulon buergerianum by HP20, ODS, Sephadex LH-20 and MCI Gel CHP-20 column chromatographic methods. Their structures were identified by spectroscopic and chemical approaches as 6-methoxyquercetin-3-O-(2'''-vanilloyl)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1), syringaresinol-4'-O-β-D-glucopyranoside (2), rutin (3), 1-O-feruloylglycerol (4), 1, 2-benzenediol (5), vomifoliol (6), β-D-(6-O-trans-feruloyl) fructofuranosyl-α-D-O-glucopyranosied (7), dihydroferulic acid (8), guanosine (9) and quercetin-3-O-β-gentiobioside (10). The compound 1 is a new compound, the compounds 2 and 4-10 were obtained from Eriocaulon genus for the first time, and the compound 3 was isolated from this plant for the first time. Molecular docking study showed that 1 is a potential inhibitor of TNF-α. The compound 1 was evaluated for their anti-inflammatory activities in vitro, and 1 showed significant inhibitory activity against TNF-α production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells at the concentrations of 1, 10 and 100 μmol·L-1.
Obesity has become an important inducer of many public diseases such as diabetes, endocrine disorders, and so on. Anti-obesity treatment has become a hot topic. Inhibiting fat synthesis and promoting fat decomposition are important ways of drug anti-obesity treatment. With the in-depth study of the distribution, morphology and function of adipose tissue, brown adipose tissue containing multi-compartment fat drops and rich mitochondria have attracted people's attention. Beige adipocytes which are similar to brown adipocytes in morphology and function have aroused great interest, such cells can be transformed from white adipocytes by external stimulation or browning agents. This process is called "white fat browning". The expression of promoting energy consumption proteins in these cells increase, so that the function of adipocytes changes from energy storage to energy consumption to increase excessive energy consumption in the body and reduce lipid accumulation. The browning of white adipose tissue has brought new ideas for obesity treatment, but the systemic administration of browning agent has the risk of adverse reactions to non-target tissues such as heart and central nervous system, which limits its application in inducing white fat browning. Browning agents to white adipose tissue can reduce its adverse reactions and improve its bioavailability by constructing a drug delivery system targeting white adipose tissue. In this review, the mechanism on browning of white adipose tissue, the commonly used browning agents and the targeted delivery carriers that induce browning of white adipose tissue are summarized.
With the in-depth study on the gut microflora, the impact of intestinal bacteria on human health has attracted more and more attention. It has become a research hotspot in life science and medicine, and is considered as an important target of disease control. Prebiotics can regulate the composition and function of intestinal flora and then improve host health. Carbohydrate is the most basic prebiotic. Its unique physiochemical characteristics and gut microbiota-regulating ability make it a promising ingredient for achieving drug target delivery and intestinal health promotion. In this paper, different kinds of prebiotics and their regulation mechanism of intestinal bacteria were illuminated. Moreover, the research progress of carbohydrate prebiotics in drug delivery system was elucidated, and its application prospect is prospected, so as to provide reference for related research.
Cirsium souliei (Asteraceae) is a perennial medicinal herb of Cirsium with important medicinal and ecological values. Here, we sequenced the complete chloroplast (cp) genome of C. souliei based on high-throughput sequencing technology, then assembled and annotated it, and analysed the structure and characteristics of the cp genome. The result indicated that the cp genome of C. souliei was a typical quadripartite circular structure of 152 470 bp in length, and GC content was 37.7%. The cp genome of C. souliei encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Meanwhile, we detected 188 simple sequence repeats (SSR) loci in the cp genome, which were mainly composed of mononucleotide repeats. Codon bias analysis showed that leucine (Leu) was the highest amino acids with frequency (10.51%), and there were 30 codons with the value of relative synonymous codon usage (RSCU) above one, of which mostly ended with A/U. Additionally, the result from phylogenetic analysis based on 46 cp genomes of Carduoideae showed that C. souliei and C. vulgare were sister species, and had the closest relationship with 100% bootstrap within Cirsium. This study provides theoretical basis for future studying genetic diversity, population genetic structure, systematics and evolution, and speciation mechanism.
The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E2) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.
A randomized, open, fasting, single dose, two sequence, two cycle and double cross administration trial design was adopted. Took the test or reference efavirenz tablets of 200 mg orally in a single time. The plasma concentration of efavirenz in healthy subjects was determined by LC-MS/MS. WinNonLin8.1 software was used to calculate the main pharmacokinetic parameters of efavirenz and to evaluate the bioequivalence. The main pharmacokinetic parameters within 72 h: tmax were 2.574 ± 0.871 and 2.808 ± 0.912 h; Cmax were 1 586.732 ± 424.538 and 1 549.518 ± 366.086 ng·mL-1; AUC0-72 h were 28 464.672 ± 5 682.518 and 27 828.826 ± 5 082.487 h·ng·mL-1; t1/2 were 63.524 ± 26.037 and 58.748 ± 20.950 h; λz were 0.013 ± 0.006 and 0.013 ± 0.005 h-1. The main bioequivalence indicators were as follows: The 90% confidence interval of Cmax was 95.62%-107.15%, and the geometric mean ratio was 101.22%; The 90% confidence interval of AUC0-72 h was 100.43%-104.38%, and the geometric mean ratio was 102.38%. The results showed that the main pharmacokinetic parameters of the test drug and the reference drug were similar, and the two preparations had bioequivalence. This human bioequivalence clinical study was approved by the drug clinical trials ethics committee of the Second Hospital of Anhui Medical University (ethics approval No.: YW2021-110).
Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.