Streptozotocin (stz)

The raw materials and drugs included cholesterol, propylthiouracil, lard, Tween 80, propylene glycol, and streptozotocin (Beijing Solarbio Science and Technology Co., Ltd., China). Rabbit anti-polyclonal CX3CR1, FKN, was purchased from Abcam, UK; rabbit anti-polyclonal NR2A and NR2B antibodies were purchased from CST, USA, while GAPDH was purchased from Proteintech, USA. streptozotocin and dexamethasone (Dex) were purchased from Saint Louis, MO, USA. IL-1β, interleukin-6 (IL-6), interleukin-8 (IL-8), and TNF-α enzyme-linked immunosorbent assay (ELISA) kits were purchased from Jingtian Biological Technology Limited Company, Shanghai, China. cholesterol (CT), corticosterone (CORT), corticotropin (ACTH), and hypothalamic corticotropin-releasing hormone (CRH) ELISA kits were from R&D Systems, Minnesota, USA. Dulbecco's modified eagle medium/nutrient mixture F-12 medium, B-27 culture additive (GIBCO), and fetal bovine serum were from HyClone Corporation, Logan City, Utah, United States. Triglycerides (TG), high density lipoprotein cholesterol (HLD-C), and low density lipoprotein cholesterol (LDL-C) ELISA kits were from Beijing Zhongsheng Biological Technology Limited Company, Beijing, China.

Streptozotocin (≥98%) was obtained from Solarbio Science and Technology (Beijing, China) while other chemicals and solvents of analytical grade used in this study were purchased from Sigma-Aldrich Chemical Co. (St. Louis, USA).

Wistar rats (200~250 g, male) and BALB/c mice (6~8 weeks old, female) were purchased from Vitalriver Laboratory Animal Technology Co., Ltd. (Beijing, China) and raised in controlled conditions in the Xiamen University Laboratory Animal Center. All animal experiments were carried out in accordance with the requirements of the Institutional Animal Care and Use Committee (Xiamen University, China). The ethics approval number is XMULAC20170258.
Wistar rats were used to develop the diabetic rat model. Wistar rats were intraperitoneally injected with streptozotocin (Solarbio Biotechnology Co., Ltd., Beijing, China) at a dose of 65 mg/kg. After 72 h, the blood glucose level (BGL) was measured by glucometer (One Touch, New Brunswick, NJ, USA). Rats with BGL higher than 13.8 mM/L were used in further experiments.
BALB/c mice were used to develop the psoriatic model. BALB/c mice were anesthetized with glutaraldehyde (4%, 0.1 mL/20 g). The back hair of the mice was shaved. Imiquimod (IMQ) cream of 31.25 mg (5%; Mingxin Pharmaceuticals, Chengdu, China) was topically and non-occlusively applied to the skin for 7 consecutive days to develop imiquimod-induced psoriatic mice.

A type 2 diabetes C57BL/6 mouse model was established according to previous research [36 (link)]. Fasting blood glucose levels of mice were detected on days 3, 7, 14, 22, and 30 after the injection of streptozotocin (Solarbio, China). The mice with fasting blood glucose levels higher than 16.7 mmol/L were considered as type 2 diabetic. The therapeutic effects of AW1 (1, 10, and 100 nM) on diabetic mouse full-thickness skin wounds were determined according to a previous study [26 (link)]. In short, two symmetrical full-thickness wounds (10 mm) were created on the dorsal of type 2 diabetic mice. The diabetic mice with full-thickness skin wounds were randomly divided into five groups: diabetic control (PBS), rh-bFGF (100 ng/mL), and AW1 groups (1, 10, and 100 nM). Wild-type mice with full-thickness skin wounds were used as normal control (PBS). Wounds were topically treated with PBS, rh-bFGF, or different concentrations of AW1 twice a day. Wound condition was recorded on days 0, 4, 8, 12, and 18. Wound tissues were acquired on postoperative days 3, 8, 12, and 18. Each experiment was repeated three times independently.

Adult male mice of the C57BL/6 background (SPF grade), provided by the Comparative Medical Center of Yangzhou University, were raised in the experimental animal room. In this study, 10 mice were randomly selected and fed a basal diet (5% fat), and 40 mice were fed a high-fat diet (60% fat). The feed was procured from Nantong Trofi Feed Co., Ltd. (Nantong, China). After 4 weeks, mice fed with a high-fat diet were intraperitoneally injected with streptozotocin (Solarbio, Beijing, China)-sodium citrate buffer (40 mg/kg body weight/day) for five consecutive days, and mice fed with a basal diet were injected with the same amount of sterile sodium citrate buffer (Solarbio, Beijing, China). The mice were continuously treated according to the above feeding plan until the 21st week. At week 21, mice with fasting blood glucose (FBG) levels ≥ 11.1 mmol/L were randomly divided into 4 groups, namely diabetic model control (MC), low-dose TFs (LTFs), high-dose TFs (HTFs), and metformin (Met; Squibb Pharmaceutical, Shanghai, China) as a positive control. From weeks 21 to 30, mice in each group were intragastrically administered TFs or sterile water following the regimen shown in Table 1. TFs (>80% of purity) were obtained from Dehe Biotechnology Co., Ltd. (Wuxi, China).