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.

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.

This paper aims to investigate the regulatory mechanism of blood-activating and stasis-dissipating drugs on fecal metabolic characteristics of rhubarb-peach kernel in mice with adenomyosis (AM) using fecal metabolome method. Adenomyosis was modeled by pituitary transplantation, and after the end of modeling administration, fecal samples were collected from mice. Non-targeted metabolomics studies were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic characteristics of the feces of mice in each group and to find intestinal differential metabolites and potential differential metabolic pathways. The results showed that compared with the normal group, 5-hydroxy-L-tryptophan, histidine, L-acetylcarnitine, 16-hydroxy hexadecanoic acid, thromboxane B₂, etc. were significantly up-regulated, L-urobilin and prostaglandin D₃ were down-regulated in the feces of the model group, and were reversed after treatment with the rhubarb-peach kernel. The results of metabolic pathway enrichment analysis showed that tryptophan metabolism and histidine metabolism were the main intervention pathways of the rhubarb-peach kernel on AM intestinal metabolism. This study found that the underlying mechanism of the rhubarb-peach kernel in the treatment of AM is related to the intervention of intestinal metabolism of tryptophan, histidine, bile acid, choline and arachidonic acid, and the regulation of pro-inflammatory microenvironment and fatty acid metabolic homeostasis. This study has been approved by the Experimental Animal Ethics Committee of China Three Gorges University (No. 20190801).

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).

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).

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.

Cytochrome P450 reductase (CPR) is essential for the electron transport chain of cytochrome P450s, playing an indispensable role in electron transfer in vivo. In this study, one cDNA encoding cytochrome P450 reductase (Ascpr1) was identified from the callus of Aquilaria sinensis. Ascpr1 contains an open reading frame of 2 124 bp. The deduced protein is composed of 707 amino acids, with a predicted molecular weight of 78.82 kD. Phylogenetic analysis revealed that AsCPR1 is a type Ⅱ CPR protein closely related to the CPR from Theobroma cacao. Transmembrane prediction using TMHMM 2.0 indicated that the amino acids 52-71 of AsCPR1 comprise a transmembrane region. After truncating of 67 amino acid residues from N-terminal, the truncated AsCPR1 was successfully expressed in E. coli Transetta (DE3). Further purification of the recombinant AsCPR1 by affinity chromatography and determination of the enzymatic activity allowed the reducing ability of AsCPR1 to cytochrome C in vitro. The results pave the way for further study on the synthesis of defensive chemicals involved in P450s and the functions of CPR in self-defense of A. sinensis.

In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R² = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f₁ and similarity factor f₂ were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.

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.

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.