Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

Dose of deferasirox correlates with its effects, which differ between low-risk myelodysplastic syndrome and aplastic anaemia.

WHAT IS KNOWN AND OBJECTIVE: Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) often need transfusions, which may accelerate iron overload. The aim of this study was to evaluate the efficacy, safety and dose-effect relationships of deferasirox (DFX) in patients with low-risk MDS and AA who were refractory to regular treatment in a real-world setting. METHODS: Patient data were recorded, and dose-effect relationships of DFX were calculated after the first 6 months. Total annual exposure to DFX was calculated after 12 months and expressed as the accumulated exposure time at a dosage of 20 mg/kg/day. RESULTS AND DISCUSSION: Sixty-one patients with low-risk MDS and 51 with AA were enrolled. The minimum dosage of DFX needed for a significant serum ferritin (SF) decrease was 20 mg/kg/day at 6 months, and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/day by 12 months for patients with low-risk MDS. For patients with AA, the minimum dosage was 10 mg/kg/day at 6 months, and the minimum accumulation had to reach 3 months at 20 mg/kg/day by 12 months. With the same exposure, significant improvements in haematological parameters were also observed in AA. Lower liver enzymes compared with baseline were observed. Gastrointestinal disorders and elevated serum creatinine were the most common side effects. Higher exposure to DFX correlated with longer overall survival (OS). WHAT IS NEW AND CONCLUSION: A significant decrease in SF and an improvement in haematologic parameters, organ function and even OS can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA.

Deciphering the Effective Constituents and Mechanisms of Portulaca oleracea L. for Treating NASH via Integrating Bioinformatics Analysis and Experimental Pharmacology.

Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. Portulaca oleracea L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, via integrating bioinformatics analysis and experimental pharmacology both in vitro and in vivo. The phenotypes and mechanisms of POL were carefully investigated by performing a set of in vivo and in vitro experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including FASN, CPT1a, SERBP1c, ACC1, and SCD1. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-α, IL-6, and IL-1ß. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH via down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.

Role of keratinocytes and immune cells in the anti-inflammatory effects of Tripterygium wilfordii Hook. f. in a murine model of psoriasis.

BACKGROUND: Tripterygium wilfordii Hook. f. (TwHf) belonging to the Celastraceae family is widely used for psoriasis treatment, especially in topical therapy in Chinese traditional medicine. PURPOSE: In this study, we investigated the anti-psoriatic effects of topical administration of Tripterygium wilfordii Hook. f. root decoction (TwHf-RD), as well as its safety and potential mechanisms of action in vivo and in vitro. METHODS: Psoriasis-like lesions were induced in mice using imiquimod (IMQ). The liver and kidney function and the pathological changes in the liver, kidney, and spleen were measured using ELISA and hematoxylin and eosin (H&E) staining after TwHf-RD treatment. H&E staining was used to determine the optimum concentration of TwHf-RD. The expression levels of ki67 and apoptosis related-factors in vivo and in vitro were measured by immunohistochemical staining, flow cytometry, and western blotting. Immunocyte differentiation and pro-inflammatory cytokine (IL-17A, IL-17F, IL-10, IL-22, IL-23, IFN-γ, and TNF-α) expression levels were determined by flow cytometry and RT-qPCR. RESULTS: TwHf-RD treatment attenuated skin inflammation, inhibited keratinocyte (KC) proliferation, increased the levels of apoptosis factors, and influenced the differentiation and inflammatory response of T lymphocytes and regulatory T cells in mice. In vitro experiments proved that Tripterygium wilfordii Hook. f. root extract (TwHf-RE) regulates the proliferation and apoptosis of PAM212 cells. CONCLUSION: TwHf-RD alleviates IMQ-induced psoriasis lesions by regulating the proliferation and apoptosis of KC and immune cells and by inhibiting immunocyte differentiation and pro-inflammatory cytokine expression.

Uncovering the mechanism of Jueyin granules in the treatment of psoriasis using network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Our clinical practice demonstrated that Jueyin granules (JYG) benefit patients with mild to moderate psoriasis vulgaris without apparent adverse effects. JYG have been shown to inhibit epidermal proliferation in an imiquimod (IMQ)-induced psoriasis-like mouse model, as well as keratinocyte proliferation. Moreover, JYG causes no acute or chronic toxicity in animal models. However, its related molecular mechanism has still not been elucidated. AIM OF THE STUDY: To assess the mechanism of JYG against psoriasis. MATERIALS AND METHODS: This study combined network pharmacology analysis with experiments to investigate the mechanism of JYG against psoriasis. First, the molecular docking technology was used to construct the network of medicinal materials-core active plant ingredients-core targets and identify possible drug targets. Next, high-performance liquid chromatography (HPLC) was used for quality control of JYG. Finally, a mice model of psoriasis was used to further verify the effects of JYG. RESULTS: (1) Molecular docking analysis of network pharmacology revealed that the therapeutic effects of JYG on psoriasis might be achieved through Vitamin D Receptor (VDR) effects. (2) The concentrations of chlorogenic acid and paeoniflorin were determined using HPLC to establish quality control of JYG. (3) JYG ameliorated pathological characteristics that included in vivo reductions in erythema, scale, and infiltration scores of back and ear lesions in IMQ-induced psoriasis-like mice. Moreover, a reduced number of PCNA-positive and Ki67-positive cells were observed in the epidermis of JYG-treated lesions. JYG also reduced inflammation (interleukin (IL)-17, IL-23) in the peripheral blood of IMQ-induced psoriasis-like mice. As expected, JYG was found to upregulate VDR expression and downregulate p-STAT3 expression in the IMQ group, which may contribute to its mechanism against psoriasis. CONCLUSION: Overall, this study clarifies the mechanism of JYG against psoriasis and provides evidence to support its clinical use.

Simultaneous Determination of Fangchinoline and Tetrandrine in Qi-Fang-Xi-Bi-Granules by RP-HPLC.

Knee Osteoarthritis is one of the most common diseases of elder worldwide. Qi-Fang-Xi-Bi-Granules (QFXBG) is a new Chinese medicine granules employed for the treatment of Knee Osteoarthritis. Fangchinoline (FAN) and tetrandrine (TET) are used as targets of quality control of QFXBG. A simple, practical high-performance liquid chromatographic method was developed for the simultaneous quantitation of FAN and TET in Stephaniae tetrandrae radix and QFXBG. The analysis was performed on a Athena C18 column (250 × 4.6 mm, 5 µm) with mobile phase of methanol-water (65 : 35, v/v, pH 3.0, adjusted by glacial acetic acid) containing 1.0 g/L sodium 1-octanesulfonate. This method was validated in terms of linearity, precision, accuracy and recovery. Results showed that this method had good linearity with R(2) at >0.999. The limit of detection and limit of quantification for FAN were 0.13 and 0.35 mg/L, while for TET were 0.28 and 0.76 mg/L, respectively. The relative standard deviations of precision were 0.1-1.3% for intraday and 0.5-2.4% for interday. The recovery was 94.56-98.81% of FAN and 94.07-99.12% of TET, respectively. The chromatographic analytical time was 14 min. This method was successfully applied for the quantitative analysis of FAN and TET in Stephaniae tetrandrae radix and QFXBG, so that it could be extended to quality control of QFXGB in commercial.