Echinacoside hampers malignant progression of breast cancer MCF-7 cells by modulating AKR1B10/ERK signal transduction / 中国中药杂志

This study analyzes the impact of echinacoside(ECH) in the proliferation, metastasis and adriamycin(ADR) resistance of breast cancer(BC) MCF-7 cells via the modulation of aldo-keto reductase family 1 member 10(AKR1B10)/extracellular signal-regulated kinase(ERK) pathway. The chemical structure of ECH was firstly confirmed. MCF-7 cells were treated with different concentration(0, 10, 20, 40 μg·mL~(-1)) of ECH for 48 h. Western blot was used to analyze expression of AKR1B10/ERK pathway-associated proteins and cell counting kit-8(CCK-8) assay to determine cell viability. MCF-7 cells were collected and classified into control group, ECH group, ECH + Ov-NC group, and ECH + Ov-AKR1B10 group. Then Western blot was employed to analyze the expression of AKR1B10/ERK pathway-associated proteins. CCK-8 and 5-ethynyl-2'-deoxyuridine(EdU) assay were used to examine cell proliferation. Cell migration was appraised with scratch assay, Transwell assay, and Western blot. Eventually, MCF-7 cells were treated with ADR for 48 h to induce ADR resistance. Cell viability was tested by CCK-8 assay and cell apoptosis was estimated based on terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay and Western blot. Based on Protein Data Bank(PDB) and molecular docking, the binding affinity of ECH to AKR1B10 was assessed. Various doses of ECH decreased the expression of AKR1B10/ERK pathway-associated proteins in a dose-dependent manner and declined cell viability compared with the control group. Compared with the control group, 40 μg·mL~(-1) ECH blocked the AKR1B10/ERK pathway in MCF-7 cells and inhibited the proliferation, metastasis and ADR resistance of the cells. Compared with the ECH + Ov-NC group, ECH + Ov-AKR1B10 group showed the recovery of some biological behaviors of MCF-7 cells. ECH also targeted AKR1B10. ECH can inhibit the proliferation, metastasis, and ADR resistance of BC cells by blocking AKR1B10/ERK pathway.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Cytoprotective Effect of Dietary Squalene Supplementation on Experimentally Induced Cardiomyopathy in Rats

Background: Adriamycin is a broadspectrum, potent, older chemotherapy drug and antineoplastic agent used in the treatment of several cancers such as solid tumours, leukaemias, and lymphomas, playing a major role in cancer chemotherapy. Long-term use of this drug results in congestive heart failure and to overcome this effect dietary squalene intake reduces the adverse effects of adriamycin-mediated cardiotoxicity and cellular oxidative stress. Methods: The current study aims to investigate the cytoprotective effects of dietary squalene supplementation on adriamycin-induced cardiomyopathy in rats in terms of alterations in Troponin T, homocysteine, diagnostic marker enzymes, and cardiac tissue histology. Results: The findings show that a 1.5 percent dose of dietary squalene supplementation for 21 days reduced adriamycin-induced changes in homocysteine, troponin T, diagnostic marker enzymes, and lesions in cardiac tissues. Conclusion: The outcomes of the study specified squalene's cytoprotective action which stabilizes membranes against adriamycin-induced oxidative membrane degradation, which is primarily responsible for heart cell irreversible necrosis.

Astragalus polysaccharides affects multidrug resistance gene 1 and P-glycoprotein 170 in adriamycin nephropathy rats via regulating microRNA-16/NF-κB axis / 中南大学学报(医学版)

OBJECTIVES@#Nephrotic syndrome is a common disease of the urinary system. The aim of this study is to explore the effect of astragalus polysaccharides (APS) on multidrug resistance gene 1 (MDR1) and P-glycoprotein 170 (P-gp170) in adriamycin nephropathy rats and the underlying mechanisms.@*METHODS@#A total of 72 male Wistar rats were divided into a control group, a model group, an APS low-dose group, an APS high-dose group, an APS+micro RNA (miR)-16 antagomir group and an APS+miR-16 antagomir control group, with 12 rats in each group. Urine protein (UP) was detected by urine analyzer, and serum cholesterol (CHOL), albumin (ALB), blood urea nitrogen (BUN), and creatinine (SCr) were detected by automatic biochemical analyzer; serum interleukin-6 (IL-6), IL-1β, tumor necrosis factor α (TNF-α) levels were detected by ELISA kit; the morphological changes of kidney tissues were observed by HE staining; the levels of miR-16 and MDR1 mRNA in kidney tissues were detected by real-time RT-PCR; the expression levels of NF-κB p65, p-NF-κB p65, and P-gp170 protein in kidney tissues were detected by Western blotting; and dual luciferase was used to verify the relationship between miR-16 and NF-κB.@*RESULTS@#The renal tissue structure of rats in the control group was normal without inflammatory cell infiltration. The renal glomeruli of rats in the model group were mildly congested, capillary stenosis or occlusion, and inflammatory cell infiltration was obvious. The rats in the low-dose and high-dose APS groups had no obvious glomerular congestion, the proliferation of mesangial cells was significantly reduced, and the inflammatory cells were reduced. Compared with the high-dose APS group and the APS+miR-16 antagomir control group, there were more severe renal tissue structure damages in the APS + miR-16 antagomir group. Compared with the control group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 in the model group were significantly increased (all P<0.05); the levels of ALB and miR-16 were significantly decreased (both P<0.05). Compared with the model group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of pNF-κB p65 and P-gp170 in the low-dose and high-dose APS groups were significant decreased (all P<0.05); and the levels of ALB and miR-16 were significantly increased (both P<0.05). Compared with APS+miR-16 antagomir control group, the UP, CHOL, BUN, SCr, IL-6, IL-1β, and TNF-α levels, MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 were significantly increased (all P<0.05). The levels of ALB and miR-16 were significantly decreased in the APS+miR-16 antagomir group compared with the APS+miR-16 antagomir control group (both P<0.05).@*CONCLUSIONS@#APS can regulate the miR-16/NF-κB signaling pathway, thereby affecting the levels of MDR1 and P-gp170, and reducing the inflammation in the kidney tissues in the adriamycin nephropathy rats.

Serum metabolomic study of Shenfu decoction on adriamycin-induced cardiomyopathy in mice / 药学实践杂志

Objective To study the reversal effect of Shenfu decoction（SFD）on adriamycin-induced cardiomyopathy and explore its mechanism by using serum metabolomic technology. Methods The BALB/c mouse model of cardiomyopathy induced by adriamycin was established. The corresponding intervention was given. The serum lactate dehydrogenase（LDH）and creatine phosphatase isoenzyme MB（CK-MB）were measured. The ejection fraction (EF) and shortening fraction (FS) were measured by echocardiography. Mouse serum was collected for gas chromatography-mass spectrometry (GC-MS) analysis. The data obtained was analyzed by multivariate and univariate statistical analysis to compare the changes of endogenous metabolites in the serum of mice in the normal group, model group and Shenfu decoction treatment group, to find the potential biomarkers of Shenfu decoction to reverse the adriamycin-induced cardiomyopathy. Metabolic pathway analysis was used to explore the targeted metabolic pathway of Shenfu decoction. Results The levels of serum LDH and CK-MB in the model group were increased significantly, and the values of EF and FS decreased significantly, indicating that the model was successfully established. The above indicators were significantly improved after treatment with Shenfu decoction. 13 potential biomarkers of adriamycin-induced cardiomyopathy were identified by metabonomic analysis, and Shenfu decoction had significant reversal effect on 11 metabolites. Metabolic pathway analysis showed that the synthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism, phenylalanine metabolism, tricarboxylic acid cycle and dicarboxylic acid metabolism were the main targeted metabolic pathways of Shenfu decoction. Conclusion Shenfu decoction can reverse adriamycin-induced cardiomyopathy by regulating the unbalanced synthesis of phenylalanine, tyrosine and tryptophan, as well as the metabolism of arachidonic acid, phenylalanine, dicarboxylic acid and tricarboxylic acid cycle.

Effect of MiR-155 Knockout Mediated by Dual sgRNAs on Drug Sensitivity of FLT3-ITD+AML / 中国实验血液学杂志

OBJECTIVE@#Two sgRNAs transfected FLT3-ITD+AML cell line MV411 with different binding sites were introduced into CRISPR/cas9 to obtain MV411 cells with miR-155 gene knockout. To compare the efficiency of miR-155 gene knockout by single and double sgRNA transfection and their effects on cell phenotypes.@*METHODS@#The lentiviral vectors were generated containing either single sgRNA or dual sgRNAs and packaged into lentivirus particles. PCR was conducted to measure gene editing efficiency, and miR-155 expression was evaluated by qPCR. CCK-8 assay was used to evaluate the cell proliferation, and calculate drug sensitivity of cells to adriamycin and quizartinib. Annexin V-APC/7-AAD staining was used to label cell apoptosis induced by adriamycin and quizartinib.@*RESULTS@#In the dual sgRNAs transfected cells, a cleavage band could be observed, meaning the success of gene editing. Compared with the single sgRNA transfected MV411 cells, the expression level of mature miR-155-5p was lower in the dual sgRNA transfected cells. And, dual sgRNA transfected MV411 were more sensitive to adriamycin and quizartinib with lower IC50 and higher apoptosis rate.@*CONCLUSION@#The inhibition rate of miR-155 gene expression transfected by dual sgRNA is higher than that by single sgRNA. Dual sgRNA transfection can inhibit cell proliferation, reverse drug resistance, and induce apoptosis more significantly. Compared with single sgRNA transfection, dual sgRNA transfection is a highly efficient gene editing scheme.

Effects of vinorelbine combined with adriamycin on breast cancer MCF-7 cells and related mechanisms / 中华内分泌外科杂志

Objective:To investigate the in vitro anti-cancer effect of Vinorelbine (NVB) combined with adriamycin (PLD) on human breast cancer MCF-7 cells and related mechanisms.Methods:The effects of NVB and PLD alone or in combination on the proliferation of breast cancer cells were detected by CCK-8 experiment. Flow cytometry was used to detect cell apoptosis and changes in reactive oxygen species (ROS) levels. Western blot experiment was carried out to detect protein expression.Results:The results of CCK-8 showed that compared with the blank control group, the inhibition rates of the vinorelbine treatment group, the adriamycin treatment group and the combined treatment group were 27.6%, 31.2% and 65.4%, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.005 vs 0.001) . The results of flow cytometry showed that the proportion of apoptotic cells in each group was 3.54%, 16.95%, 15.01% and 32.24%, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.006 vs 0.005) . The levels of reactive oxygen species in each group were 1, 1.03, 1.06 and 1.57, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.008 vs 0.007) . Western blot results showed that the expression of p-ERK and p-STAT3 decreased after the combination of NVB and PLD, which inhibited the ERK/STAT3 signaling pathway. Conclusions:The combination of NVB and PLD can promote the apoptosis of breast cancer cells and inhibit the proliferation of breast cancer cells with high efficiency and low toxicity. Its mechanism of action may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the ERK/STAT3 pathway.

Protective Effect of Wenyang Huoxue Huatan Prescription on Cardiotoxicity Induced by Anthracyclines / 中国实验方剂学杂志

Objective:To study the protective effect of the Wenyang Huoxue Huatan prescription （WYHXHT） on cardiotoxicity induced by adriamycin. Method:SD rats were randomly divided into the following six groups： a normal control group， an adriamycin model group， a low-dose （4.86 g·kg^-1） WYHXHT group， a middle-dose （9.72 g·kg^-1） WYHXHT group， a high-dose （19.44 g·kg^-1） WYHXHT group， and a dexrazoxane group. Except for the normal control group， the rats in other groups received intraperitoneal injection of 2.5 mg·kg^-1 adriamycin， once a week for six weeks， with a cumulative dose of 15 mg·kg^-1. The normal control group， the adriamycin model group， and the dexrazoxane group received 10 mL·kg^-1 normal saline daily by gavage. In the dexrazoxane group， the rats were subjected to intraperitoneal injection of 25 mg·kg^-1 dexrazoxane 30 min before doxorubicin administration， once a week for six weeks. The general condition of rats was observed and their body weight was monitored. A high-resolution micro-ultrasound imaging system was used to detect rat cardiac function. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes of myocardial tissues of rats. Western blot was used to detect the protein expression of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， the mammalian homolog of yeast Atg6 （Beclin-1）， and p62 protein in rat myocardial tissues. Result:Compared with the normal control group， rats in the adriamycin model group showed dull fur， reduced food intake and activity， loose stool， low energy， and slow response. Besides， it also displayed reduced body weight （<italic>P</italic><0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （<italic>P</italic><0.01）， myocardial cell degeneration， edema， rupture， and dissolution， expansion of myocardial interstitium， uneven staining of myocardial fiber， visible inflammatory cell infiltration， up-regulated expression of Beclin-1 and LC3Ⅱ in rat myocardial tissues （<italic>P</italic><0.01）， and down-regulated p62 expression （<italic>P</italic><0.01）. Compared with the adriamycin model group， the medium- and high-dose WYHXHT groups exhibited increased body weight， LVEF， and LVFS （<italic>P</italic><0.01）， relieved pathological injury of myocardial tissues， down-regulated expression of LC3Ⅱ and Beclin-1 （<italic>P</italic><0.05，<italic>P</italic><0.01）， and up-regulated expression of p62 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:WYHXHT can effectively prevent and treat adriamycin-induced cardiotoxicity， and its effect may be related to the inhibition of myocardial cell autophagy. The effect is dominant in the high-dose group.

Immunomodulatory effect of adriamycin in mouse 4T1 model of breast cancer / 生物工程学报

To explore the immunomodulatory effect of adriamycin on 4T1 breast cancer. We used a tandem mass tag-based quantitative proteomic method to detect differential proteins in breast cancer tissues, and multiple bioinformatics databases to analyze the differentially expressed proteins in the proteome. Also, we used enzyme-linked immunosorbent assay to detect the effects of adriamycin on helper T cells 1 and 2 in breast cancer tissues, and flow cytometry to detect CD4+ T cells, CD8+ T cells and regulatory T cells. We discovered the immunomodulatory targets of adriamycin in differential proteins. In total 170 differential proteins were significantly up-regulated, whereas 58 were markedly down-regulated. In addition, 73 proteins were involved in immune regulation. Kyoto encyclopedia of genes and genomes enriched important protein pathways related to cytokines and factor receptors, interleukin 17 pathway and cancer transcriptional regulatory pathways. These pathways and important differential proteins related to immunomodulatory functions were ultimately regulated by adriamycin on CD4+ T cells, CD8+ T cells and regulatory T cells, thereby affecting the prognosis of breast cancer. Moreover, adriamycin significantly increased interleukin 2, CD4+ T and CD8+ T (P<0.01) and markedly reduced regulatory T cells (P<0.05). The function of adriamycin against triple-negative breast cancer was closely related to the immunoregulation process of the differential proteins Ighm, Igkc, S100A8, S100A9 and Tmsb4x. Adriamycin could regulate the content of helper T cells 1 cytokines, CD4+ T and CD8+ T lymphocytes in breast cancer and reduce the number of regulatory T cells to produce immunomodulatory effects.

p-Coumaric acid alleviates adriamycin-induced hepatotoxicity in rats

Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats. Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured. Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL-1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage. Conclusions: p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

P-Coumaric acid alleviates adriamycin-induced hepatotoxicity in rats

Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats. Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured. Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL- 1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage. Conclusions: P-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

Effect of Puta on in vitro anticancer activity of Shataputi AbhrakBhasma on lung, leukemia and prostate cancer cell lines

Background: Rasashastra needs to be upgraded using the technological advances, with regards to drugprocessing, development and therapeutics. The potential of Rasaaushadhis need to be explored by subjecting them against newer life threatening diseases like cancer where contemporary medicine haslimitations. Abhrak Bhasma, one of the drugs of Rasashastra, has some peculiar attributes. According toclassical Rasashastra texts, Shataputi Abhrak Bhasma is regarded as a Rasayan, whose efficacy is in directproportion to the number of Putas. Thus increasing number of Putas not only has a significant effect onthe physical, analytical aspects but also the therapeutic effect of the Abhrak Bhasma.Objectives: To screen in vitro anticancer activity of Abhrak Bhasma at various stages of Putas (20, 50, 100).To evaluate and thus validate the principle from classical Rasashastra texts, which explains direct relationof number of Putas with therapeutic efficacy.Materials and methods: Shataputi Abhrak Bhasma, at various stages of its preparation was subjected toin vitro anticancer activity on three different cancer cell lines (LungHOP62, LeukemiaU937, ProstateDU145) at Tata Memorial Centre- Advanced Centre for Treatment, Research Education in Cancer, NaviMumbai. SRB assay was followed to evaluate the anti-proliferative activity.Results: It was found that Abhrak Bhasma shows concentration dependent positive in vitro anticanceractivity on all three cell lines with highly significant activity on prostate cancer cell lines. Anticanceractivity of Abhrak Bhasma is in the order 100 Puti > 50 Puti > 20 Puti. Shataputi Abhrak Bhasma hadmaximum activity on prostate cancer cell lines almost equivalent to positive control drug adriamycin.Conclusion: The in vitro anticancer activity of Shataputi Abhrak Bhasma increases with increasing numberof Putas, thus revalidating the direct relation between number of Putas and efficacy of the drug.© 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V

Effect of New Shengmai Decoction on apoptosis and protein expression of Bax, Bcl-2, and Caspase-3 of cardiomyocyte induced by adriamycin / 中草药

Objective: To observe the reversal and prevention effect of New Shengmai Decoction on the rats’ cardiomyocyte apoptosis induced by adriamycin, and provide the experimental foundation basis for the clinical treatment of myocardial injury induced by adriamycin. Method: The rat models with cardiomyocyte apoptosis were established by adriamycin. Forty male SD rats were divided randomly into four groups, including the normal group, the adriamycin model group, the captopril group and the New Shengmai Decoction group. During the experiment, the mental state, activity, feeding, hair color and other conditions of the rats were observed. After 6 weeks of treatment, the cardiac function and left ventricular hypertrophy of rats were measured and the pathological changes of myocardium were observed by HE staining. And the apoptosis of myocardial cells was observed by TUNEL staining and protein expressions of Caspase-3, Bcl-2, and Bax were detected by immunohistochemistry. Results: Compared with the control group, the cardiac function of the model group was significantly decreased. Compared with the model group, the cardiac function of rats after the different drugs’ treatment could be improved in the different degrees and the effect of the New Shengmai Decoction group was significant. Compared with the control group, the heart body ratio, left ventricular hypertrophy index and myocardial cell apoptosis index in the model group were all significantly increased. Compared with the model group, the captopril group and the New Shengmai Decoction group ameliorated cardiac hypertrophy and myocardial cell apoptosis in rats. Compared with the control group, the expression level of bcl-2 protein in the model group was decreased, while the expression level of Bax and Caspase-3 protein was increased. Compared with the model group, captopril and the New Shengmai Decoction increased the expression level of bcl-2 protein and decreased the expression level of Bax and Caspase-3 protein. Conclusion: The New Shengmai Decoction can improve the cardiac function and lessen cardiomyocyte apoptosis of rats. It can also decrease the expression of protein Caspase-3 in the cardiac muscle of rats or inhibit its activity. In order to restrain cardiomyocyte apoptosis, the New Shengmai Decoction can increase the expression of protein Bcl-2 and decrease the expression of protein Bax through improving the expression of Bcl-2/Bax in the cardiac muscle of rats.

Tumor neuroectodérmico recidivante. A propósito de un caso y revisión bibliográfica / Recurrent neuroectodermal tumor. A case report and literatura review

Resumen ANTECEDENTES: La relación entre cáncer y embarazo supone 0.07% de las complicaciones gestacionales. Cuando estas situaciones coinciden el tratamiento del tumor se dificulta. El tumor neuroectodérmico primitivo es una neoplasia relacionada con el sarcoma de Ewing y su incidencia es excepcional durante el embarazo. CASO CLÍNICO: Paciente de 34 años, con 36.3 semanas de embarazo, que ingresó a la unidad hospitalaria por dolor abdominal irradiado al miembro inferior derecho. A la exploración física se palpó una tumoración de gran dimensión en la fosa iliaca derecha. La ecografía abdominal objetivó una imagen compatible con un mioma. La resonancia magnética reportó una masa de 16 x 13 x 17 cm, retroperitoneal, paravertebral, coincidente con tumor neuroectodérmico, sarcoma y tumor neurogénico. La paciente tuvo parto eutócico, sin administración de analgesia epidural, del que nació una niña de 2950 g, con Apgar 8-9. Se efectuó una biopsia por aspiración con aguja gruesa, que reportó un tumor neuroectodérmico primitivo. El tratamiento consistió en quimioterapia con protocolo VAC (vincristina, dactinomicina y ciclofosfamida [14 ciclos]) y adriamicina (6 a 8 ciclos de inducción). Actualmente padece dolor neuropático en la pierna derecha y permanece en rehabilitación, con tratamiento médico. CONCLUSIONES: Los tumores neuroectodérmicos primitivos son neoplasias excepcionales durante el embarazo. Se requieren estudios complementarios para conocer la relación exacta entre este tipo de tumores y el embarazo, y de esta forma establecer el protocolo de tratamiento adecuado.

Abstract BACKGROUND: The relationship between cancer and pregnancy accounts for 0.07% of gestational complications. This aspect makes treatment difficult and has a negative impact on pregnant patients. The primitive neuroectodermal tumor is a neoplasm related to Ewing's sarcoma and its incidence is exceptional during pregnancy. CLINICAL CASE: A 34-year-old patient, 36.3 weeks pregnant, who was admitted to the hospital unit due to abdominal pain radiating to the right lower limb. Physical examination revealed a large tumor in the right iliac fossa. The abdominal ultrasound showed an image compatible with a myoma. Magnetic resonance imaging revealed a mass of 16 x 13 x 17 cm, retroperitoneal, paravertebral, coinciding with neuroectodermal tumor, sarcoma and neurogenic tumor. The patient had eutocic delivery, without administration of epidural analgesia, from which a girl of 2950 g was born, and Apgar 8/9. An aspiration biopsy was performed with a thick needle, which reported a primitive neuroectodermal tumor. The treatment consisted of chemotherapy with VAC protocol (vincristine, dactinomycin and cyclophosphamide [14 cycles]) and adriamycin (6 to 8 induction cycles). He currently suffers from neuropathic pain in the right leg and remains in rehabilitation, with medical treatment. CONCLUSIONS: Primitive neuroectodermal tumors are exceptional neoplasms during pregnancy. Complementary studies are required to know the exact relationship between this type of tumors and pregnancy, and in this way establish the appropriate treatment strategy.

Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Effects of low-intensity pulsed ultrasound on hematopoietic function in rats after combined chemotherapy with doxorubicin and cyclophosphamide / 南方医科大学学报

OBJECTIVE@#To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on hematopoietic function in rats after combined chemotherapy with doxorubicin and cyclophosphamide.@*METHODS@#Eighty rats were randomized into control group and LIPUS group (=40) for treatment with intraperitoneal injection of doxorubicin (2 mg/kg)+cyclophosphamide (20 mg/kg) for 4 consecutive days and continuous irradiation with LIPUS for 7 days following the injections, respectively. The white blood cells, red blood cells and platelets counts in each group were measured at 0, 4, 7, 9, 11, 14 and 18 days after the start of drug administration. The pathological sections of the bone marrow were examined at 0, 4 and 11 days, and the flow cytometry was performed for detecting the cell apoptosis; qPCR was performed for detecting the expressions of SCF, ICAM-1, and VCAM-1 mRNAs, and ELISA was used to detect the expressions of IL-3 and GM-CSF.@*RESULTS@#The white blood cell count was significantly higher in LIPUS group than in the control group ( < 0.05). Histopathological examination of the bone marrow revealed significantly increased hematopoietic tissue in LIPUS group ( < 0.05). Flow cytometry demonstrated an obviously lower cell apoptosis rate in the bone marrow in LIPUS group than in the control group ( < 0.05). Compared with those in the control group, the mRNA expression levels of ICAM-1 and VCAM-1 as well as the protein levels of IL-3 and GM-CSF were significantly increased in LIPUS group ( < 0.05).@*CONCLUSIONS@#LIPUS can alleviate the hematopoietic damage after combined chemotherapy with doxorubicin with cyclophosphamide probably by increasing the expressions of ICAM- 1, VCAM-1, IL- 3, and GM-CSF.

Protective Effect and Mechanism of Aqueous Extract of Perillae Folium on Adriamycin-induced Oxidative Injury in HK-2 Cell / 中国实验方剂学杂志

Objective: To investigate the protective effect of Perillae Folium with aqueous extract (PFAE) on some key factors of Adriamycin (ADR)-induced oxidative injury in human renal tubular epithelial cells(HK-2), including the survival rate, oxidative injury indexes and cell apoptosis,in order to define the underlying mechanism. Method: A model of ADR-induced HK-2 cells oxidative injury was established in vitro, then cell viability was detected by cell counting kit-8 (CCK-8) after intervention with positive reference N-acetylcysteine (NAC) or PFAE (5,15,45 g·L-1) at different concentrations. According to the morphological changes under microscopy, the optimum concentration of PFAE was screened out for the follow-up experiments. Then, the experiments were divided into six groups:blank group, ADR (0.05 g·L-1) group, PFAE (15 g·L-1) group, ADR+PFAE (0.05+15) g·L-1 group, NAC (0.81 g·L-1) group, and ADR+NAC (0.05+81) g·L-1 group. After that, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity(TAC) were measured in the cell homogenate after 24 h administration. The level of reactive oxygen species (ROS) was detected by 2',7'-dichloroflurescin diacetate (DCFH-DA) fluorescence probe. Flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to monitor the cell apoptosis. Western blot was used to observed the expressions of mitochondrial apoptosis-associated proteins, like B lymphocyte tumor-2 gene (Bcl-2), Bcl-2 related X protein (Bax), cysteine aspartate protease-9 (Caspase-9), cysteine aspartate protease-3 (Caspase-3) and poly ADP-ribose polymerase (PARP), as well as their shear bodies. In addition, the phosphorylation protein expressions of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signaling transduction pathway were detected by Western blot. Result: Compared with blank group, ADR group showed a decreased cell viability (PPPPPPPP-1. The ATC and SOD levels were increased in ADR+PFAE group and ADR+NAC group (PPConclusion: PFAE could alleviate the oxidative injury of HK-2 cells induced by ADR, and have an antioxidant effect, which inhibited cell apoptosis through mitochondrial apoptotic pathway and ERK/p38 MAPK signaling pathway.

Mechanism of Huanglian Ejiao Tang on Prevention and Treatment of Myocardial Injury Induced by Anthracycline Chemotherapy Drugs / 中国实验方剂学杂志

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (PPPPPConclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.

Progress in Research of Kangxianling Decoction in Delaying Renal Fibrosis / 中国实验方剂学杂志

Renal fibrosis is a common pathological change in the later stages of all kidney diseases. It is a multi-cytokine, multi-signal pathway, multi-factor driven chronic kidney disease. It includes renal interstitial fibrosis, tubular sclerosis and glomerular sclerosis, which eventually leads to chronic renal failure. From health through injury to loss of function, the disease process is closely related to the degree of deterioration of renal function and the prognosis of chronic kidney disease. There is no effective western medicine for the treatment of renal fibrosis. Professor HE Liqun from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine has summarized the Kangxianling decoction through decades of long-term practical experience. It has the effects in strengthening the spleen and replenishing Qi, clearing away dampness and heat, promoting blood circulation and removing phlegm, and strengthening turbidity. It is composed of Salviae Miltiorrhizae Radix et Rhizoma 15 g, Persicae Semen 12 g, Angelicae Sinensis Radix 12 g, Achyranthis Bidentatae Radix 9 g, Rhei Radix et Rhizoma 15 g. Kangxianling can affect the synthesis and secretion of cytokines and inflammatory factors by expanding blood vessels, and can improve renal tubular fibrosis. It has a good multi-channel, multi-target and multi-directional protective effect on renal function. It also can delay the progress of chronic renal fibrosis by significantly alleviating such symptoms as fatigue and edema in patients with chronic renal fibrosis, and reducing serum creatinine, urea nitrogen and urine protein. In this paper, 5/6 nephrectomy, ischemia reperfusion injury, adriamycin-induced nephropathy, unilateral ureteral obstruction and other different modeling methods are listed. The mechanism of Kangxianling decoction in antagonizing renal fibrosis is discussed and summarized, which further provided new ideas and directions for future clinical and scientific research.

Effects of PTEN Combined with Adriamycin on the Proliferation, Migration and Invasion of Adriamycin in Non Hodgkin lymphoma Raji Cells / 中国药学杂志

OBJECTIVE: To investigate the inhibitiom effect of PTEN(gene of phosphate and tension homology deleted on chromsome ten) combined with adriamycin on proliferation, migration and invasion of non-Hodgkin lymphoma cell line Raji in vitro. METHODS: Cell proliferation was determined by MTT in Raji cells response to adriamycin with different concentrations. Transwell assay was performed to evaluate the effects of adriamycin and PTEN on migration and invasion of Raji cells. RT-qPCR was conducted to measure the expression of PTEN in Raji cells after adriamycin treatment. RESULTS: Adriamycin significantly inhibited the proliferation of Raji cells in a concentration dependent manner (r=-0.925, P<0.001). Adriamycin inhibited invasion and migration in Raji cells. Moreover, adriamycin promoted the expression of PTEN. Overexpression of PTEN markedly suppressed invasion and migration in Raji cells. The combination of adriamycin and PTEN strikingly decreased the proliferation, invasion and migration of Raji cells. CONCLUSION: Adriamycin and PTEN would inhibite the proliferation, invasion and migration of Raji cells. PTEN drastically enhances the inhibition of adriamycin on the proliferation, migration and invasion of Raji cells.