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Cinnamomum cassia Presl is a tropical aromatic evergreen tree of the Lauraceae family, commonly used in traditional Chinese medicine. It is also a traditional spice, widely used around the world. This paper summarizes the achievements of modern research on C. cassia, including the traditional uses, phytochemistry, pharmacology and toxicology. In addition, this review also discusses some significant issues and the potential direction of future C. cassia research. More than 160 chemicals have been separated and identified from C. cassia. The main constituents of C. cassia are terpenoids, phenylpropanoids, glycosides, etc. Modern studies have confirmed that C. cassia has a wide range of pharmacological effects, including antitumour, anti-inflammatory and analgesic, anti-diabetic and anti-obesity, antibacterial and antiviral, cardiovascular protective, cytoprotective, neuroprotective, immunoregulatory effects, anti-tyrosinase activity and other effects. However, the modern studies of C. cassia are still not complete and more in-depth investigations need to be conducted in alimentotherapy, health product, toxicity and side effects, and more bioactive components and potential pharmacological effects need to be explored in the future.

Limonin is a natural tetracyclic triterpenoid compound, which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron chinense Schneid., and Coptis chinensis Franch. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the pharmacology, toxicity, and pharmacokinetics of limonin. Therefore, this review aimed to provide the latest information on the pharmacology, toxicity, and pharmacokinetics of limonin, exploring the therapeutic potential of this compound and looking for ways to improve efficacy and bioavailability. Limonin has a wide spectrum of pharmacological effects, including anti-cancer, anti-inflammatory and analgesic, anti-bacterial and anti-virus, anti-oxidation, liver protection properties. However, limonin has also been shown to lead to hepatotoxicity, renal toxicity, and genetic damage. Moreover, limonin also has complex impacts on hepatic metabolic enzyme. Pharmacokinetic studies have demonstrated that limonin has poor bioavailability, and the reduction, hydrolysis, and methylation are the main metabolic pathways of limonin. We also found that the position and group of the substituents of limonin are key in affecting pharmacological activity and bioavailability. However, some issues still exist, such as the mechanism of antioxidant activity of limonin not being clear. In addition, there are few studies on the toxicity mechanism of limonin, and the effects of limonin concentration on pharmacological effects and toxicity are not clear, and no researchers have reported any ways in which to reduce the toxicity of limonin. Therefore, future research directions include the mechanism of antioxidant activity of limonin, how the concentration of limonin affects pharmacological effects and toxicity, finding ways to reduce the toxicity of limonin, and structural modification of limonin—one of the key methods necessary to enhance pharmacological activity and bioavailability.

Zingiberis Rhizoma Recens (ZRR, the fresh rhizoma of Zingiber officinale Roscoe) is a widely used traditional Chinese medicine (TCM). It is also a traditional spice, widely used around the world. The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology of Zingiberis Rhizoma Recens. In addition, this review also discusses some significant issues and the potential direction of future research on Zingiberis Rhizoma Recens. More than 100 chemical compounds have been isolated from Zingiberis Rhizoma Recens, including gingerols, essential oils, diarylheptanoids, and other compounds. Modern studies have confirmed that Zingiberis Rhizoma Recens has pharmacological effects on the nervous system and cardiovascular and cerebrovascular systems, as well as antiemetic, antibacterial, antitumor, anti-inflammatory, and antioxidant effects. However, the modern studies of Zingiberis Rhizoma Recens are still not complete and more bioactive components and potential pharmacological effects need to be explored in the future. There is no unified standard to evaluate the quality and clinical efficacy of Zingiberis Rhizoma Recens. Therefore, we should establish reasonable, accurate, and reliable quality control standards to make better use of Zingiberis Rhizoma Recens.

Background: Curcumae blood Radix (Yujin) has been widely used to treat Qi stagnation and stasis in TCM. According to the Chinese Pharmacopoeia, the tuberous roots of Curcuma longed L. (i.e., Huangsiyujin, HSYJ) is one of the major species of Yujin. According to the processing theory of TCM, stir-frying HSYJ with vinegar might strengthen the effect of dispersing stagnated hepatoqi to relieve pain, and stir-frying HSYJ with wine might strengthen the effect of promoting blood circulation in order to remove blood stasis. However, the mechanism for the enhancement of clinical efficacy by processing is unclear.Aim/Hypothesis: This study was aimed at evaluating the effect of different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanisms of HSYJ in treating pain caused by Qi stagnation and blood stasis. Methods:The effects of different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatment and intervention with HSYJ and its processed products, β-endorphin (β-EP) and 5hydroxytryptamine (5-HT) were measured by ELISA, and the expression of c-fos was evaluated by immunohistochemistry.Results: After stir-frying with vinegar or wine, the extract yield and curcumin content increased. Compared with model group, raw HSYJ could significantly improve the abnormality of 5-HT in plasma (P < 0.05) and β-EP in brain (P < 0.01). Stir-frying HSYJ with vinegar or wine could significantly improve the abnormality of 5-HT in plasma, β-EP in brain, and the expression of c-fos (P < 0.01). Stir-frying HSYJ with vinegar could also significantly increase the level of β-EP in plasma (P < 0.05).Frontiers in Pharmacology | www.frontiersin.org 1 March 2020 | Volume 11 | Article 242Chen et al. Huangsiyujin Regulates Pain-Related SubstancesConclusion: These results showed that different processing methods have certain effects on the chemical constituents of HSYJ, mainly in increasing the decoction rate and curcumin content. HSYJ and its processed products can reduce 5-HT levels, increase β-EP levels, and inhibit the expression of c-fos in model rats. The effects of stir-frying HSYJ with vinegar on β-EP levels in plasma was superior to others.

SAPO-37 with a faujasite-type structure was studied by X-ray diffraction at high temperature and high pressure. A similar degree of negative thermal expansion (NTE) was observed for SAPO-37 with respect to siliceous faujasite with a v(303-773 K) = 210.7 6 10 26 K 21 . This similarity can be linked to the important role of oxygen displacement in proposed NTE mechanisms. SAPO-37 is more compressible than other faujasites, with a bulk modulus of 18(1) GPa. SAPO-37 also undergoes pressure-induced amorphisation at lower pressures. These results indicate that changes in chemical composition can strongly modify the stability and compressibility of the faujasite network.

Abstract. The aim of the present study was to investigate the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) patients from eastern coastal China and to determine whether it is correlated with the clinicopathological features of PTCs with or without current Hashimoto thyroiditis (HT). The BRAF V600E mutation status was analyzed in 206 thyroid nodules of 154 patients undergoing thyroidectomy using polymerase chain reaction and bi-directional sequencing. Multivariate analysis was performed to investigate the association of the BRAF V600E mutation with clinicopathological features. Thyroid nodules were classified as PTC, nodular goiter (NG), adenomatoid nodule, adenoma and HT. The BRAF V600E mutation was observed in 61.5% of PTCs analyzed; it was also detected in one normal tissue adjacent to PTC and one NG. One patient exhibited double mutations in the BRAF gene; the BRAF V600E mutation in the PTC lesion and the BRAF K601E mutation in the contralateral NG lesion. Patients harboring the BRAF V600E mutation had higher thyroid stimulating hormone levels (2.453±1.464 vs. 1.966±1.296 mIU/l), a reduced occurrence of papillary thyroid microcarcinoma (55.0 vs. 88%), and a higher occurrence of lymph node metastasis (LNM; 42.5 vs. 16.0%) compared with those with wild-type BRAF (all P<0.05). Binary logistic regression analysis revealed that the BRAF V600E mutation was associated with LNM of PTC (hazard ratio, 5.051; 95% confidence interval, 1.068-23.893; P= 0.041). Conversely, no association was identified between the BRAF V600E mutation and HT (38.5 vs. 67.3%, χ 2 =3.656, P=0.056). Thus, in regional PTCs, the BRAF V600E mutation was prevalent, suggesting that it may be an early and phenotypically defining molecular event in PTC, and may represent an independent factor that predicts LNM.

Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study established a rat OA model by intra-articular (IA) injection of mono-iodoacetate (1.5 mg) and weekly treated by IA administration of FLL at 100 μg/mL for 4 weeks. Thermal withdrawal latency, mechanical withdrawal threshold, and spontaneous activity were tested for evaluation of pain behavior, and histopathological (HE, SO, and ABH staining) and immunohistochemical (Col2, Col10, and MMP13) analyses were conducted for observation of cartilage degradation. In vitro effect of FLL on chondrocytes was evaluated by MTT assay and qPCR analysis. Moreover, HPLC analysis was performed to determine its chemoprofile. The pain behavioral data showed that FLL attenuated joint pain hypersensitivity by increasing thresholds of mechanical allodynia and thermal hyperalgesia as well as spontaneous activity. The histopathological result showed that FLL reversed OA cartilage degradation by protecting chondrocytes and extracellular matrix in cartilage, and the immunohistochemical analysis revealed its molecular actions on protein expressions of MMP13, Col2, and Col10 in cartilage. The MTT assay showed its proliferative effects on chondrocytes, and qPCR assay clarified its mechanism associated with gene expressions of Mmp13, Col2, Col10, Adamts5, Aggrecan, and Runx2 in TNF-α treated chondrocytes. Our results revealed an anti-OA effect of FLL on pain behavior and cartilage degradation in OA rats and clarified a molecular mechanism in association with the suppression of chondrocyte hypertrophy and catabolism. IA FLL can be regarded as novel and promising option for OA therapy.