The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

To explore the mechanism hydroxysafflor yellow A (HSYA) biosynthesis and regulation, the effect of methyl jasmonate (MeJA) treatment on gene expression related to the biosynthesis of hydroxysafflor yellow A (HSYA) was analyzed, and expression differences in genes involved in HSYA biosynthesis in safflower of different colors was quantified. MeJA at concentrations of 0, 50, 100, and 200 μmol·L^-1 was sprayed onto safflower florets to determine the optimal concentration of MeJA. Safflower was treated with 100 μmol·L^-1 MeJA and florets were harvested 0, 3, 6, 12 and 24 h after treatment. The content of MeJA was determined by high performance liquid chromatography (HPLC). RNA was extracted from safflower florets treated with 100 μmol·L^-1 MeJA for 6 h. The transcription of key genes involved in the biosynthesis of HSYA was quantified by qRT-PCR and differentially expressed genes were identified. The content of HSYA increased after treatment with MeJA, with 100 μmol·L^-1 MeJA treatment for 6 h having the greatest effect on HSYA accumulation. qRT-PCR results showed that MeJA could significantly increase the transcription of HSYA biosynthesis genes including PAL2, PAL4, 4CL2, 4CL4, 4CL5, CHS3, CHS4 and CHI2. The content of HSYA differed between safflowers of different colors with a trend of red > orange-yellow > yellow > white. The results of qRT-PCR showed that the expression of CHS1 and CHI2 in red, orange and yellow safflower was significantly higher than that in white safflower. These results indicate that MeJA promotes the accumulation of HSYA by up-regulating the expression of genes involved in the biosynthesis of HSYA such as PAL2, PAL4, 4CL2, 4CL4, 4CL5, CHS3, CHS4 and CHI2, and the variation of HSYA content in safflower of different colors was related to a difference in the level of expression of CHS1 and CHI2.

Reactive nitrogen species (RNS) affects intracellular redox balance and induces post-translational modification of proteins. Moreover, RNS, as the signal molecule, participates in the transduction of cellular signals under physiological conditions. However, excessive RNS can induce nitrosative stress and then damage cells, and thereby may play a role in the tumor initiation and progression. Thus, we discussed the role of RNS under physiological conditions and the tumor microenvironment, which may provide some novel ideas for the development of new drugs and the treatment of diseases.

Characterization of the polysaccharides and monosaccharides of Bupleurum chinense was undertaken to identify differences in the Bupleurum chinense's sugar profiles, so as to provide a basis for the identification of different varieties. High performance liquid chromatography (HPLC) was used to generate chromatograms of the total polysaccharides of Bupleurum using an Evaporation Light Detector (ELSD), and a monosaccharide chromatogram was generated using a UV-detector (UV) following polysaccharide derivatization. The data were analyzed using SIMCA software and SPSS software to distinguish different varieties of Bupleurum. The results show that the yield of polysaccharides from Bupleurum falcatum is the highest, while the yield of polysaccharides from Bupleurum chinense is the lowest. The polysaccharide spectrum shows that the molecular weights of the polysaccharides in different Bupleurum differ, and their percentages of the total peak area are also different. The four Bupleurum polysaccharides are composed of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, but differ in length. The ratio of glucose to arabinose in Bupleurum chinense, Bupleurum scorzonerifolium, Bupleurum falcatum and Bupleurum marginatum var. stenophyllum is: 3.0-4.0, 5.5-7.0, 12.0-17.0, 9.0-12.0. In this study, a sugar profile technique was developed to provide a new method for the identification of different varieties of Bupleurum.

The scientific world has witnessed multiple outstanding breakthroughs in the field of traditional Chinese medicine and natural product derived drugs during 2015-2020. The research by Prof. Tu Youyou on artemisinin gained her as one of the winners of Nobel Prize in Physiology or Medicine in 2015, has also aroused profound impetus in the investigation of traditional Chinese medicine and natural product drugs. Mori ramulus alkaloids tablets and GV-971 capsules have been approved by National Medical Products Administration (NMPA) for clinical application. Some of the important research findings were selected as "Top 10 major medical advances" in China, and a plenty of research articles were accepted by world top publications such as Nature, Science, New England Journal of Medicine, as well as Lancet, etc. The current review summarized and commented on the research highlights of traditional Chinese medicine and natural drugs published in world top journals from 2015 to 2020, including the major progresses in the sub-divided areas of chemistry, molecular pharmacognosy, pharmacology and toxicology, as well as pharmaceutics. This report aims to follow and review the leading research and hot spots in fields of traditional Chinese medicine and natural drugs, and to provide prospects and inspirations in the interdisciplinary areas based on our preliminary analyses.

Macrophages play an important role in the pathogenesis of rheumatoid arthritis (RA). Previously, studies have shown that changes in the metabolism of glucose, choline, amino acids and lipids in macrophages of patients with RA can lead to the accumulation of metabolic intermediates which can act as inflammatory signaling molecules to aggravate the inflammation and cause complications. Therefore, a full understanding of the metabolic process of macrophages in RA patients will lay the foundation for macrophage-targeted therapy of RA. In this review, not only the role of macrophage abnormal metabolism in the pathogenesis of RA but also the research progress on macrophage-targeted drugs in RA treatment will be discussed.

In recent years the interaction between host and gut microbiota has attracted increasing attention. However, intestinal flora dysbiosis may lead to many diseases, and there is increasing evidence that the intestinal microbiota in patients with chronic kidney disease (CKD) is associated with the pathophysiological status of the host. "Gut-kidney axis" provides a better explanation of the two-way communication between intestinal flora and CKD. Impaired kidney function leads to dysbiosis of intestinal flora and an altered intestinal flora can damage the intestinal mucosal barrier and facilitate the entry into the bloodstream of harmful bacteria, which can induce chronic inflammation and thus accelerate renal injury. In addition, the accumulation of nephrotoxic metabolites from an altered intestinal flora can aggravate CKD in the "gut-kidney axis". Among them, p-cresol sulfate, indoxyl sulfate and trimethylamine oxide are the most widely studied metabolites of nephrotoxicity, and their renal toxicity has been widely confirmed in basic research and clinical studies. Current studies show that the intestinal microbiota-metabolite network is closely related to the occurrence and development of chronic kidney disease. Thus, intervention in the intestinal microbiota may provide a new approach to the prevention and treatment of chronic kidney disease.

The chemical constituents from ethyl acetate extract of Gleditsiae spina were isolated and purified by various chromatographic methods such as MCI gel CHP-20, ODS, Sephadex LH-20, silica gel and semi-preparative HPLC. Seven lignans were isolated and identified by spectroscopic data analyses as (7R, 8S, 7'E, 7''S, 8''R)-buddlenol P (1), (+)-syringaresinol (2), (+)-isolariciresinol (3), (7S, 8R)-cedrusin (4), (7S, 8R)-4, 9, 9'-trihydroxy-3, 3'-dimethoxy-7, 8-dihydrobenzofuran-1'-propylneolignan (5), 3', 4-O-dimethylcedrusin (6), balanophonin (7). Among them, compound 1 is a new lignan, compounds 2-7 are isolated from the Gleditsia L. for the first time. MTT method was used to investigate the effect of compounds 2-7 on LPS-induced injury of NRK-52e cells. As a result, compounds 2, 3 and 7 exhibit protective effects against LPS-induced damage to NRK-52e cells.

Circadian rhythm is an internal regulatory mechanism that allows organisms to adapt to circadian changes in the external environment, and can regulate the body's steady state by affecting the metabolic pathways of multiple organs. When exogenous factors such as eating time, worktime changes, and sleep disturbances cause the body's circadian rhythm to be disrupted, the risk of developing metabolic syndrome is significantly increased. This article explores the relationship between circadian rhythm and body metabolism and summarizes the molecular mechanisms by which circadian rhythm regulates the digestive system, liver and bile acid production, and kidney function. We review research progress on intervention in the circadian rhythm by traditional Chinese medicine and provide a reasonable and valuable basis for follow-up studies on the role of traditional Chinese medicine in research on the molecular mechanisms of regulation of circadian rhythm.

G protein-coupled receptor 119 (GPR119) has been a promising target for the treatment of type 2 diabetes. It can not only directly promote insulin secretion, but also indirectly increase insulin secretion by stimulating the release of glucose-dependent GIP/CLP-1 without causing hypoglycemia. The remarkable advantages of small molecule GPR119 agonists make it one of the research hotspots for the development of type 2 diabetes drugs. This article reviews the anti-diabetic small molecules based on the GPR119 target in the past five years.