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.

UDP-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.

Equisetin (EQST) belongs to polyketide (PKS)-nonribosomal peptide synthetase (NRPS) type compound with an inhibitory effect of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme activity. This study investigated anti-obesity effect and insulin resistance improvement effect of EQST on high-fat diet (HFD)-induced ob/ob mice model. EQST treatment effectively reduced the body weight gain, fat weight gain and blood lipid content of model mice. All animal experiments were approved by the Medical Ethics Committee of Capital Institute of Pediatrics. EQST alleviated adipose tissue expansion and hepatic ballooning degeneration of model mice, and also effectively controlled the blood glucose content after glucose load and insulin load, showed a significant improvement in obesity and insulin resistance. EQST inhibited adipogenic proteins fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ), and upregulated thermogenic protein (uncoupling protein 1, UCP1) through suppressing 11β-HSD1 protein expression. In addition, EQST widely upregulates mitochondrial respiratory metabolism related proteins in adipose tissue and may improve insulin resistance through phosphatidylinositol-3-kinase (PI3K) pathway. Therefore, EQST plays an anti-obesity role by promoting adipose tissue thermogenesis and improving insulin resistance, which may provide reliable clues for improving obesity and diabetes.

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.

IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition of autoimmune etiology in recent twenty years, mainly manifesting as mass-forming lesions in single or multiple organs. In the past, it was often missed or misdiagnosed as inflammation or tumor. Patients may die from multiple organ failure due to end-stage fibrosis if they are not treated promptly. However, the number of clinically confirmed cases has gradually increased with the improvement of diagnostic level in recent years, and these patients have benefited greatly after receiving early treatment. Although patients generally respond well to traditional immunosuppressors including glucocorticoids and disease-modifying anti-rheumatic drugs, refractory and recurrent cases, even patients with glucocorticoid contraindication are common. Important mechanistic insights have been derived from studies of B-cell depletion therapy, but greater awareness of the pathophysiology of IgG4-RD is still badly needed to identify novel therapeutic targets. In this article, we reviewed the pathogenesis progress and promising therapy of IgG4-RD to seek better clinical management of IgG4-RD.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, and its incidence and mortality are among the top three of all malignant tumors. In recent years, CRC is becoming more common in younger patients. Currently, surgery is the main or first treatment of early stage CRC, however, up to 50% patients have recurrence and metastasis post-surgery. While chemotherapy and radiotherapy are often used as adjuvant treatment after surgery or as main treatment options for late stage CRC, they usually induce severe adverse effects. Safe and effective treatments for CRC are still lacking. Therefore, it is essential to discover new therapies for CRC. Neuropilin 1 (NRP1), as a transmembrane glycoprotein, is reported to highly express in CRC, and its overexpression is demonstrated to be closely related to the occurrence and development of CRC. NRP1 is involved in angiogenesis, tumor growth, autophagy, and lipid metabolism, which is expected to be a potential new target for the treatment of CRC. This paper reviews the role of NRP1 in CRC, including its molecular structure, expression in CRC, as well as its connection with autophagy and metabolism. The regulatory factors of NRP1 in CRC were introduced, including vascular endothelial growth factor (VEGF), semaphorin 3A (SEMA3A), transforming growth factor-β (TGF-β), etc. The potential intervention strategies of CRC targeting NRP1 were summarized in order to provide reference for the diagnosis and prevention of CRC.

This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica. The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) and Masson staining, the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were detected, and transforming growth factor β1 (TGF-β1), Smad family member 3 (Smad3), α-smooth muscle actin (α-SMA) pathway index expression in lung tissue was detected by fluorescence quantitative PCR. UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them. The results showed that compared with the model group, the medium (1.5 g·kg^-1) and high (3.0 g·kg^-1) doses of Amygdalus mongolica total extract could significantly reduce the lung index, significantly increase the activity of SOD in serum and lung tissue, reduce the degree of alveolar inflammation and pulmonary fibrosis, and reduce MDA in serum and lung tissue, and significantly reduce TGF-β1, Smad3, α-SMA mRNA expression in lung tissue. Serum metabolomics profile analysis identified 25 significantly different metabolites, the Amygdalus mongolica total extract can participate in linoleic acid metabolism, glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers: lysoPE(0∶0/22∶5(4Z, 7Z, 10Z, 13Z, 16Z)), lysoPC(20∶0/0∶0), PC(20∶5(5Z, 8Z, 11Z, 14Z, 17Z)/15∶0), 12, 13-dihydroxy-9-octadecenoic acid (12, 13-DHOME), 9, 10-dihydroxy-12-octadecenoic acid (9, 10-DHOME) to affect pulmonary fibrosis. This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats, and provided a reference basis for the clinical application of Amygdalus mongolica. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No.20170315).

In order to clarify the pharmacodynamic substances and mechanism of Xiangju Preparations (Xiangju Tablets, Xiangju Drops) in the treatment of rhinitis and sinusitis, the multi-level network integration analysis of "ingredients-targets-pathways" was conducted. 137 chemical constituents were identified in Xiangju Preparations by high pressure liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-QTOF/MS) for the first time. Network pharmacology analysis was performed on 59 potential active components. The results of network pharmacology analysis demonstrated that the medicinal ingredients in Xiangju Preparations included caffeic acid, senkyunolide F, rosmarinic acid, ligustilide, prim-O-glucosylcimifugin, linarin, magnolin, luteolin, senkyunolide I and gallic acid. These ingredients act on the crucial targets of tumor necrosis factor (TNF), interleukin 1B (IL1B), protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3 (STAT3) and participate in the regulation of advanced glycosylation end products-receptor of AGEs (AGE-RAGE), TNF, nuclear factor kappa B (NF-κB), and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathways to effectively treat rhinitis and sinusitis. The excellent binding performance between above 10 active components and 5 key target proteins was further confirmed by molecular docking, indicating that these 10 ingredients are pharmacodynamic substances of Xiangju preparations. In conclusion, this study preliminarily clarified the effective components and mechanism of Xiangju preparations in the treatment of rhinitis and sinusitis, and provided a theoretical basis for the clinical application of Xiangju preparations.

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).