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Combinatory effect of hesperetin and mesenchymal stem cells on the deteriorated lipid profile,heart and kidney functions and antioxidant activity in STZ-induced diabetic rats

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BIOCELL 2020年第1期44卷 27-39页

作者： Osama M.AHMED Mohamed A.hasSAN Ablaa S.SALEH experimental Obesity and Diabetes Research Lab(EODRL) Physiology DivisionZoology DepartmentFaculty of ScienceBeni-Suef UniversityPO 62521Beni-SuefEgypt Biochemistry department Faculty of ScienceBeni-Suef UniversityPO 62521Beni-SuefEgypt

This study aimed to assess the effect of hesperetin and/or bone marrow-derived mesenchymal stem cells(BM-MSCs)on disturbed lipid profile,heart and kidney functions,oxidative stress and antioxidant defense system in streptozotocin(STZ)-induced diabetic *** 1 diabetes mellitus(T1DM)was induced in male Wistar rats by injecting 40 mg/kg body weight(b.w.)STZ dissolved in citrate buffer(pH 4.5).The diabetic rats were treated with hesperetin orally administered at dose 20 mg/kg b.w.,BM-MSCs intravenously injected at a dose of 1 x 106 cells/rat/week and their combination for 6 *** diabetic rats exhibited lipid abnormalities manifested by elevated serum levels of total cholesterol,triglycerides,LDL-cholesterol and VLDL-cholesterol and lowered HDL-cholesterol as well as elevated liver cholesterol and triglycerides content in association with the resultant fasting and postprandial hyperglycemia and insulin *** heart function biomarkers including CK-MB,AST and LDH activities as well as levels of kidney function parameters,creatinine,and urea,were significantly raised in the serum of diabetic *** changes were concomitant with abnormal redox balance represented by elevated lipid peroxidation,decreased glutathione content,and suppressed antioxidant enzyme activities in both heart and kidney of diabetic *** previous deleterious alterations were significantly ameliorated after the treatment of diabetic rats with hesperetin and BM-MSCs singly or in combination;the treatment with hesperetin together with BM-MSCs was the most *** on these findings,it can be concluded that the use of hesperetin with BM-MSCs may have more additive therapeutic value than their uses singly in *** addition,the ameliorative effects of hesperetin and BM-MSCs on lipid profile and heart and kidney functions in diabetic rats may be mediated,at least in part,via their suppressive effects on oxidative stress and ameliorative effects on the antioxidant defense system

关键词： BM-MSCs Hesperetin Streptozotocin-induced diabetes

Regression of liver metastases of occult carcinoid tumor with slow release Lanreotide therapy

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World Journal of Gastroenterology 2005年第13期11卷 2041-2044页

作者： Marta Bondanelli Maria Rosaria Ambrosio Maria Chiara Zatelli Luigi Cavazzini Laura Al Jandali Rifa'y Ettore C.degli Uberti department of Biomedical Sciences and Advanced Therapies-Section of Endocrinology department of experimental and Diagnostic Medicine

Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation index, immunoreactiviy for somatostatin receptor (SSTR)-l, 2, 3 and 5 and positive octreoscan. Urinary 5-hydroxyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanreotide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a clear-cut long-lasting anti-proliferative effect of SR-LAN on liver metastases of occult carcinoid with high proliferation index and immunoreactivity for SSTR-1, 2, 3, and 5. Immunohistochemistry for SSTRs could be a suitable method for the selection of patients with metastatic carcinoid that may benefit from SST analog therapy.

关键词： Carcinoid Somatostatin analogs Somatostatin receptors

Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

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Acta Pharmacologica Sinica 2005年第9期26卷 1025-1033页

作者： Danila CORADINI Annalisa SPERANZA UO Tumor Biology and experimental Therapy department of experimental Oncology Istituto Nazionale per lo Studio e la Cura dei Tumori 20133 Milan Italy UO Tumor Biology and experimental Therapy department of experimental Oncology Istituto Nazionale per lo Studio e la Cura dei Tumori 20133 Milan Italy

Hepatocellular carcinoma(HCC)is one of the most common cancers in the *** resection has been considered the optimal treatment approach,but onlya small proportion of patients are suitable candidates for surgery,and the relapserate is *** to prevent recurrence,including chemoemboliza-tionbefore and adjuvant therapy after surgery,have proven to have a limited benefit;liver transplantation is successful in treating limited-stage HCC because only aminority of patients qualify for ***,new therapeutic strat-egies are urgently *** in addition to the classical genetic mecha-nisms of deletion or inactivating point mutations,epigenetic alterations,such ashyperacetylation of the chromatin-associated histones(responsible for genesilencing),are believed to be involved in the development and progression ofHCC,novel compounds endowed with a histone deacetylase(HDAC)inhibitoryactivity are an attractive therapeutic *** particular,pre-clinical resultsobtained using HA-But,an HDAC inhibitor in which butyric acid residues areesterified to a hyaluronic acid backbone and characterized by a high affinity forthe membrane receptor CD44,indicated that this class of compounds may repre-sent a promising approach for hepatocellular carcinoma treatment.

关键词： hepatocellular carcinoma histone deace-tylase inhibitors cancer therapy

Comparative assessment of natural and synthetic reproductive inhibitors in Oreochromis niloticus

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International Journal of Agricultural and Biological Engineering 2024年第5期17卷 284-292页

作者： Rafia Jamal Farkhanda Asad Shabana Naz Syed Makhdoom Hussain department of zoology Government College University FaisalabadFaisalabadPunjabPakistan

Nowadays, natural sources of sex reversal agents are preferred over synthetic ones in fish farming due to their reliability and economic value. This study compared the effectiveness of 17α-methyltestosterone (MT), Carica papaya seed meal (PSM), and common carp testes (CCT) with tilapia (Oreochromis niloticus) in terms of sex reversal, hematological parameters, gonadal histology, enzymatic activity, and overall growth. A 90-day trial was conducted with 560 tilapia fry (2- 3 days old) distributed into one control and six treatment aquaria, each with two replicates. Fries were fed with a control diet (T0) or one of six experimental diets (T1-T6) containing different MT, PSM, or CCT levels for 30 days, followed by the control diet for 60 days. MT induced the highest male proportion (85% and 75% in T2 and T1, respectively), while PSM and CCT enhanced tilapia’s growth and carcass composition. Histological analysis revealed gonadal deformities in MT and PSM treatments, which might lead to sterility. The gonadosomatic index (GSI) was reduced in natural treatments as compared with synthetic ones. Hematological parameters did not show any adverse effects of PSM and CCT. Protease and amylase activities were higher in PSM and CCT than in MT, indicating better digestion and feed absorption. PSM and CCT are biodegradable, locally available, and eco-friendly alternatives to synthetic hormones to change sex in tilapia. Natural sources (plant and animal by-products) are preferable to synthetic sources as they are less expensive and control prolific breeding in tilapia.

关键词： sex reversal natural reproductive inhibitors synthetic reproductive inhibitors Oreochromis niloticus Carica papaya

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

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World Journal of Gastrointestinal Oncology 2016年第1期8卷 30-39页

作者： Roberta Gaziano Gabriella Moroni Cristina Buè Martino Tony Miele Paola Sinibaldi-Vallebona Francesca Pica department of experimental Medicine and Surgery University of Rome Tor Vergata

Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice.

关键词： Sanguinarine Cancer Apoptosis Cell-cycle Chemotherapy

Evidence on neuroprotective properties of coenzyme Q10 in the treatment of glaucoma

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Neural Regeneration Research 2019年第2期14卷 197-200页

作者： Alessio Martucci Carlo Nucci Ophthalmology Unit Department of Experimental Medicine University of Rome Tor Vergata

Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve head, and specific visual field defects. Clinical evidence shows that intraocular pressure is the major risk factor of the treatable disease. However, in some patients, glaucoma develops and continues to progress despite normal intraocular pressure values, suggesting that other risk factors are involved in the disease. Consequently, neuroprotective treatments, focused on preventing retinal ganglion cells death by acting on different therapeutic strategies but not focused on intraocular pressure reduction, has therefore become of great interest. In this contest, coenzyme Q10, showing evidence in slowing or reversing pathological changes typical of the disease, has been proposed as a potential neuroprotective agent in glaucoma. In this review, we describe the possible mechanisms of action of coenzyme Q10 and the recent evidence in literature regarding the neuroprotective activity of the molecule.

关键词： glaucoma neuroprotection retinal ganglion cells coenzyme Q10 intraocular pressure mitochondrion oral administration neurodegenerative diseases

Hepatopoietin Cn suppresses apoptosis of human hepatocellular carcinoma cells by up-regulating myeloid cell leukemia-1

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World Journal of Gastroenterology 2010年第2期16卷 193-200页

作者： Chu-Tse Wu department of experimental Hematology Beijing Institute of Radiation Medicine27 Taiping Road

AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this ***, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/ HPPCn receptor in SMMC7721 and *** cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium ***:The HPPCn was highly expressed in human HCC cells and secreted into culture medium(CM). FITC-labeled recombinant human protein(rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9%to 85.6%and 88.4%,respectively(P< 0.05).HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin ***, HPPCn could up-regulate the expression of myeloid cell leukemia-1(Mcl-1)in HCC cells via mitogen-activated protein kinase(MAPK)and sphingosine kinase-1. CONCLUSION:HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.

关键词： Hepatopoietin Cn Autocrine Hepatocellular carcinoma Apoptosis Myeloid cell leukemia-1

Prevention of DNA re-replication in eukaryotic cells

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Journal of Molecular Cell Biology 2011年第1期3卷 13-22页

作者： Lan N.Truong Xiaohua Wu department of Molecular and experimental Medicine The Scripps Research InstituteLa JollaCA 92037USA

DNA replication is a highly regulated process involving a number of licensing and replication factors that function in a carefully orchestrated manner to faithfully replicate DNA during every cell *** of proper licensing control leads to deregulated DNA replication including DNA re-replication,which can cause genome instability and *** organisms have established several conserved mechanisms to prevent DNA re-replication and to counteract its potentially harmful *** mechanisms include tightly controlled regulation of licensing factors and activation of cell cycle and DNA damage *** licensing control and its associated compromised checkpoints have both been observed in tumor cells,indicating that proper functioning of these pathways is essential for maintaining genome *** this review,we discuss the regulatory mechanisms of licensing control,the deleterious consequences when both licensing and checkpoints are compromised,and present possible mechanisms to prevent re-replication in order to maintain genome stability.

关键词： DNA re-replication cell cycle checkpoints DNA damage response Cdt1 DSB repair genome stability tumorigenesis

New tumor-associated antigen SC6 in pancreatic cancer

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World Journal of Gastroenterology 2005年第48期11卷 7671-7675页

作者： Min-Pei Liu Xiao-Zhong Guo Jian-Hua Xu Di Wang Hong-Yu Li Zhong-Min Cui Jia-Jun Zhao Li-Nan Ren department of experimental Medicine Northern Hospital Shenyang Liaoning Province China

AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb)in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal ***: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)of 41, 80, and 118 U/mL were ***: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of *** expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% ***: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of

关键词： Tumor antigen SC6 Pancreatic neoplasm Immunoradiometric assay