Erhuang quzhi compounds is one of the protecting liver and inhibiting toxin prescriptions series summarized by Jinqi Yuan and other famous doctors of traditional Chinese medicine during the long-term clinical practice. It is very effective for non-alcoholic fatty liver disease (NAFLD), but its mechanism is not clear. This research investigated mechanism of Erhuang quzhi granules (EQG) in the treatment of NAFLD. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the First Affiliated Hospital of Shihezi University. Mouse models of NAFLD were established by feeding with methionine and choline deficient diet (MCDD) for five weeks. While feeding MCDD, the treatment groups were given EQG (16.25 g·kg^-1·d^-1) and atorvastatin (ATO, 7.20 mg·kg^-1·d^-1) by gavage. The effects of EQG on serum biochemical indices, liver pathological changes, and inflammatory cytokines in mice of NAFLD were investigated. Quantitative real-time PCR (qPCR), immunocytochemistry (ICH) and Western blot assays were used to detect the levels of mRNA and protein associated with nuclear factor kappa B/Nod-like receptor protein 3 (NF-κB/NLRP3) in liver. The results showed that EQG significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and improved the level of low-density lipoprotein cholesterol (LDL-C). The result of hematoxylin-eosin (HE) staining showed that EQG reduced lipid deposition in livers of mice. Meanwhile, EQG notably decreased the levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor-α (TNF-α), and mRNA levels of NF-κB, NLRP3, IL-1β, TNF-α, down-regulated the expression of F4/80, IκB kinase β (IKKβ), NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) and inhibited the activation of NF-κB and cysteinyl aspartate specific proteinase-1 (caspase-1). These findings announced that EQG could improve NAFLD via NF-κB/NLRP3 pathway possibly, which provides a theoretical basis for the further development and utilization of EQG in clinic.

A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC₅₀) values at the nanomolar range. Compound 8d exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC₅₀ value of 156.39 nmol·L^-1 and compound 7b showed the most potent inhibition for butyrylcholinesterase with IC₅₀ value of 16.33 nmol·L^-1. Kinetic and molecular modeling studies showed that 8d targeted both the catalytic active site and the peripheral anionic site of AChE. In addition, these compounds showed low toxicity to hepatocytes, and compound 8d did not increase the level of reactive oxygen species in HepG2 cells.

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.

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.

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

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.

The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.

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.

In this study, a method for simultaneous quantitative analysis of 6 salvianolic acids and 4 tanshinones in extracts of Salviae Miltiorrhizae Radix et Rhizoma was established by ultra-high performance liquid chromatography (UHPLC). The semi-biomimetic method was applied to simulate digestion process in vitro, to explore the digestion and transport characters of oral administration through the gastrointestinal tract, and to explain the content ratio changes and bioaccessibility of active ingredients in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the 10 index components have a good linear relationship in the corresponding concentration range, and the average recovery rate was 91.35% to 105.65%. After simulated digestion in vitro, types of chemical composition in simulated gastric fluid and simulated intestinal fluid digested extracts of Salviae Miltiorrhizae Radix et Rhizoma did not change significantly. While the content ratio of salvianolic acid B and rosmarinic acid decreased, and the content ratio of protocatechuic aldehyde and danshensu increased. In the simulated gastric fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: danshensu (50.19%) > salvianolic acid B (33.44%) > lithospermic acid (27.34%) > salvianolic acid A (21.71%) > rosmarinic acid (12.31%). In the simulated intestinal fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: 15, 16-dihydrotanshinone Ⅰ (5.45%) > tanshinone Ⅰ (3.67%) > cryptotanshinone (3.29%) > tanshinone ⅡA (3.01%) > salvianolic acid A (2.39%) > lithospermic acid (1.57%) > salvianolic acid B (1.02%) > danshensu (0.41%) > rosmarinic acid (0.34%). In conclusion, the UHPLC method established in this study can be applied for accurately and sensitively detecting the contents of 6 salvianolic acids and 4 tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results of semi-biomimetic extraction showed that not all components were extracted with simulated gastric fluid and simulated intestinal fluid, especially rosmarinic acid and salvianolic acid B. Therefore, in the quality study of Salviae Miltiorrhizae Radix et Rhizoma and its extract, bioavailability should be considered at the same time when select quality markers and determine their content limits.

The bZIP (basic leucine zipper) gene family is one of the largest transcription factor families in eukaryotes, and its members play important roles in stress response, secondary metabolism, plant growth, seed development and other aspects. To investigate the biological functions of the bZIP (CsbZIP) gene in Cannabis sativa L., we systematically investigated the CsbZIP gene family using bioinformatics methods based on the whole-genome and transcriptome data. The results showed that 55 CsbZIP gene family members (CsbZIP1-CsbZIP55) were identified and distributed on 10 chromosomes, belonging to 12 subfamilies. The gene structure and protein motif distribution of the same subfamily members were similar. Segment repeats were the main reasons for the expansion of CsbZIP gene family. Cis-elements analysis showed that the promoter regions of 73 lipid synthesis genes contained G-box or A-box element. qRT-PCR showed that the relative expression levels of 7 CsbZIP genes and 7 lipid synthesis genes were relatively high in hemp seed. 7 CsbZIP genes had a significant positive correlation with 7 lipid synthesis genes. This study revealed the structural features, evolutionary patterns and expression patterns of CsbZIP, providing important clues for further study on the regulation of CsbZIP on oil metabolism of hemp seed.