Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs.

Objective To establish the determination of prim-O-glucosylcimifugin in Biyan Tablets by HPLC.Methods The HPLC determination was carried out on Diamonsil C18 column(4.6 mm? 250 mm,5 ? m).The mobile phase consisted of methanol-acetonirile-H2O(18 :12 :70) with a flow rate of 1.0 mL/min,and the ultraviolet detection wavelength was set at 254 nm.Results Prim-O-glucosylcimifugin showed a good linearity in the range of 0.1888～ 1.534 ? g with the peak area score,the coefficient was 0.9997,and the average recovery was 101.74 %(RSD=2.97 %).Conclusion The method is accurate and reliable,and can be used for the quality control of Biyan Tablets.

Objective To study the galactagogue effect of Maidang Rutong Granules on the lactation rats.Methods The milk volume,morphology of mammary gland,serum prolactin level and pituitary acidophil number in lactation rats and the growth improvement in suckling mice were observed after administrating various dosages of Maidang Rutong Granules to lactation rats by gastric gavage.Results Maidang Rutong Granules can promote the dilation and hyperplasia of acinus cavity and conduit in mammary gland,reduce the mammary interlobular fat connective tissue,significantly increase pituitary acidophil number and serum prolactin level,increase the milk volume of lactation rats and their offspring's body weight.Conclusion Maidang Rutong Granules exhibit significant galactagogue effect on lactation rats.

Objective To evaluate the effects of low blood sugar production index (LGI) combined with low blood sugar production burden (LGL) dietary intervention on blood glucose, oxidative stress and anthropometric indicators in type 2 diabetes mellitus. Methods A total of 150 cases of type 2 diabetes were randomly divided into two groups,maintain the original treatment plan of two groups,75 patients in the control group were given traditional food interchange method for dietary intervention;the experimental group of 75 patients, provide food education based on LGI+LGI food exchange method , the time period of 3 months. Fasting blood glucose (FPG)、2h postprandial blood glucose (2hPG), Glycated hemoglobin (HbAlc), Superoxide dismutase (SOD), Malondialdehyde (MDA), Vitamin C, Vitamin E, Body Mass Index (BMI), Waist circumference (WC) Upper arm muscle circumference (AMC), Triceps skin fold thickness (TSF) were observed before and after the intervention. Results There were no significant differences in blood glucose, oxidative stress and anthropometry between the two groups (P>0.05). After intervention, in the control group: FPG, 2hPG, HbAlc, SOD, MDA, Vitamin C, Vitamin E, BMI, WC, AMC, TSF were (10.27 ± 2.67) mmol/L, (11.51 ± 2.54) mmol/L, (8.78 ± 1.95)%, (322.73 ± 51.97) kU/L, (5.80 ± 1.76)μmol/L, (40.78±4.86)μmol/L, (19.33±4.79)μmol/L, (23.94±3.18) kg/m2, (89.57±10.23) cm, (24.10± 3.01) cm, (18.38 ± 3.79)mm respectively. In the experimental group: they were (8.76 ± 2.77) mmol/L, (10.63 ± 1.76) mmol/L, (7.96 ± 1.86)%, (357.29 ± 60.04) kU/L, (5.26 ± 1.33)μmol/L, (44.01 ± 7.06)μmol/L, (21.58 ± 5.25) μmol/L, (22.93 ± 2.75) kg/m2, (86.05 ± 10.79) cm, (22.75 ± 2.86) cm, (16.98 ± 4.48) mm respectively. There was significant difference between the two groups after intervention (t=2.049-3.769, all P < 0.05). In the experimental group, the improvement of blood sugar, oxidative stress and anthropometry was better than that of the control group (P < 0.05). Conclusions LGI combined with LGL diet intervention is better than the traditional method of food interchange, the blood glucose, oxidative stress and anthropometric indicators have improved, which can improve treatment efficacy in type 2 diabetes and easy for home self-management.

Aberrant activation of the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB,Akt)-mammalian target of rapamycin(mTOR) pathway is commonly observed in human cancer and is critical for cell survival, proliferation and differentiation.A variety of small molecule inhibitors targeting PI3K-Akt-mTOR pathway are under clinical studies.This review will summarize the recent studies in terms of the PI3K-Akt-mTOR signaling pathway and cancer,research progress of the antitumor activity possessed by PI3K-Akt-mTOR inhibitors,as well as the recent research in the related field conducted by our group.

Objective To investigate the chemical constituents of Citrus medica var. sareodactylis from Sichuan province, and to provide evidence for the development and utilization and quality evaluation of the medicinal material.Methods Various chromatographic techniques were used to purify the components of this herb. Compounds were identi-fied by their physical characteristics and spectral feature. Results Seven compounds were isolated from Citrus medica var. sarcodactylis, and they were identified as sibiricol (Ⅵ), 7-methylesculetin (Ⅶ), bergapten (Ⅷ), sigmasteryl acetate(Ⅸ), 5-methoxyfurfural(Ⅹ), limonin(Ⅺ), daucosterol (Ⅻ). Conclusion Compound Ⅵ, Ⅶ and Ⅸ are isolated from plants of Rutaceae for the first time.

Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and increases in incidence with aging.Low mortality and high disability rates bring huge economic and psychological burden to society and families.PD manifested as motor symptoms and non-motor symptoms.Recent studies have shown that non-motor symptoms,such as sensory disorder,are the significant symptoms in early stages of PD and influence quality of life of PD patients.This review focuses on the characteristics and electrophysiological changes of sensory disorders (olfactory,visual,auditory,vestibule function,pain,etc) in PD patients to provide help for the early diagnosis,disease monitoring and efficacy evaluation of PD.

OBJECTIVES: To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity. METHODS: C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice. RESULTS: In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice. CONCLUSIONS Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.
Male ; Humans ; Animals ; Mice ; Reactive Oxygen Species/metabolism* ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Mice, Inbred C57BL ; Apoptosis ; Poly(ADP-ribose) Polymerases/metabolism*

OBJECTIVES: To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs. METHODS: The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs. RESULTS: Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05). CONCLUSIONS Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Antineoplastic Agents/pharmacology* ; Lung Neoplasms/genetics* ; DNA Damage ; DNA ; Deubiquitinating Enzymes/genetics*

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.