Gardeniae Fructus, a traditional Chinese medicine, has significant pharmacological activities such as clearing heat and detoxifying, promoting bile secretion and protecting liver injury. It is widely used in clinical practice for treating conditions like fever-induced restlessness, damp-heat jaundice, dysuria with pain, and fire-toxin sores. Gardeniae Fructus has been included in "list of items that are both food and medicine", so it is also used as an ingredient in food and health products. However, recent toxicological studies have shown that Gardeniae Fructus has certain potential hepatotoxicity, and its improper use may pose a risk. Therefore, it is necessary to clarify the dual regulatory effects and their scientific connotations of Gardeniae Fructus on efficacy and toxicity. Based on the current progress in clinical, pharmacological and toxicological researches, this paper will discuss the characteristics and possible mechanisms of the dual effects of efficacy and toxicity of Gardeniae Fructus, and propose thoughts on the rational clinical use and scientific supervision of Gardeniae Fructus.
Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Fruit/chemistry* ; Gardenia/chemistry* ; Medicine, Chinese Traditional ; Liver/drug effects*

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).
Humans ; Antineoplastic Agents/adverse effects* ; Maximum Tolerated Dose ; Neoplasms/drug therapy* ; Neutropenia/chemically induced* ; Prospective Studies

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Animals ; Bronchoalveolar Lavage Fluid ; Cigarette Smoking ; Interleukin-17/genetics* ; Lung ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive

Objective:To observe the effect of Huayu Jiedu recipe （HYJDR） on apoptosis of gastric cancer cells， explore the mechanism of HYJDR on apoptosis of gastric cancer cells and provide experimental basis for clinical application of HYJDR. Method:Thiazolyl blue tetrazolium bromide （MTT） method was used to detect the effect of HYJDR （5，10，15，20，25，30 g·L^-1） on the activity of SGC-7901 cells and the median inhibition concentration （IC₅₀） of HYJDR on SGC-7901 cells. Propidium iodide （PI） and Hoechst double fluorescence staining were used to detect the effect of HYJDR on the apoptosis of gastric cancer SGC-7901 cells. Western blot was used to detect the effect of HYJDR on the expression of apoptosis related proteins in gastric cancer cells. Real-time polymerase chain reaction （Real-time PCR） was used to detect the effect of HYJDR on the expression of apoptosis related protein mRNA in gastric cancer cells. Result:As compared with blank group， HYJDR （>10 g·L^-1） can significantly inhibit the proliferation of gastric cancer cells. With the increase of the concentration of HYJDR， the cell viability decreased significantly obviously in a concentration-dependent manner（P<0.05）. HYJDR can significantly promote the apoptosis of gastric cancer cells. With the increase of the concentration of HYJDR， the apoptosis of gastric cancer cells gradually increased. As compared with blank group， HYJDR can obviously inhibit the expression of apoptosis-related B -cell lymphoma-2 （Bcl-2） （P<0.05）， and increase the expression of apoptosis-promoting proteins such as Bcl-2 antagonist of cell death （Bad） and Bcl-2-associated X （Bax）（P<0.05）. Real-time PCR results showed that as compared with blank group， HYJDR（5，10 g·L^-1） could effectively inhibit the expression of Bcl-2 protein mRNA in gastric cancer cells（P<0.05）， and all HYJDR groups could promote the expression level of Bad mRNA（P<0.05）. Conclusions:HYJDR can obviously promote the apoptosis of SGC-7901， and its effect is probably achieved by increasing the expression of Bad mRNA and inhibiting the expression of Bcl-2 protein.