CD73 facilitates tumor growth by upregulation of the adenosine (immunosuppressive factor) in the tumor microenvironment, however, its precise molecular mechanisms is not precisely understood. Regarding the importance of angiogenesis in tumor development and spreading, we decided to assign the anti-angiogenic effects of CD73 suppression. We used chitosan lactate (ChLa) nanoparticles (NPs) to deliver CD73-specific small interfering RNA (siRNA) into cancer cells. Our results showed that treatment of the 4T1 cells with CD73-specific siRNA-loaded NPs led to potent inhibition of cancer cell proliferation and cell cycle arrest, in vitro. This growth arrest was correlated with downregulation of angiogenesis-related molecules including vascular endothelial growth factor (VEGF)-A, VEGF-R2, interleukin (IL)-6, and transforming growth factor (TGF)-β. Moreover, administration of NPs loaded with CD73-siRNA into 4T1 breast cancer-bearing mice led to tumor regression and increased mice survival time accompanied with downregulation of angiogenesis (VEGF-A, VEGF-R2, VE-Cadherin, and CD31) and lymphangiogenesis (VEGF-C and LYVE-1)-related genes in the tumor site. Furthermore, the expression of angiogenesis promoting factors including IL-6, TGF-β, signal transducer, and activator of transcription (STAT)3, hypoxia inducible factor (HIF)-1α, and cyclooxygenase (COX)2 was decreased after the CD73 suppression in mice. Moreover, analysis of leukocytes derived from the tumor samples, spleen, and regional lymph nodes showed that they had lower capability for secretion of angiogenesis promoting factors after CD73-silencing. These results indicate that suppression of tumor development by downregulation of CD73 is in part related to angiogenesis arrest. These findings imply a promising strategy for inhibiting tumor growth accompanied with suppressing the angiogenesis process.
In recent years, the use of medicinal plants increased considerably; so that today, the use of traditional medicine, as well as medicinal plants is necessary for the aim of producing more effective drugs with fewer side effects and determining the effective doses. With the scientific name of Juglans regia, walnut plant is a medicinal plant with different properties that is considered less, despite having great therapeutic potential in the traditional medicine. The aim of this study was to review the dispersal of walnut plants, the chemical compounds, and therapeutic effects of walnuts on antioxidant activity, antidiabetic, hypolipidemic, antimicrobial, and antihypertensive activities, as well as liver protection. Data of this review study have been collected from the books and scientific articles published in databases such as Science Direct, Web of Science, Scopus, PubMed, and Scientific Information Database. While this plant having high antioxidant capabilities, walnuts are composed of many chemical compounds such as ascorbic acid, flavonoids, quercetin, and caffeic acid. Experimental studies have shown that walnuts reduced blood glucose and lipids and also decreased blood pressure. They have antioxidant, antidiabetic, antimicrobial, and liver-protective properties. The use of walnuts in traditional medicine and review of experimental studies demonstrated the presence of multiple, effective, and useful compounds which may provide the opportunity for the production of lipid-lowering, antidiabetes, and liver protective drugs. Due to the effects of walnuts on improving the complications of various diseases, the need for doing comprehensive clinical trials for the use of walnuts in the treatment of diseases is necessary.
Objective:The objective of the present investigation was to evaluate the therapeutic efficacy of mulberry leaves in an animal model of diabetes.Materials and Methods:Animals were treated with mulberry leaf extract 400 mg and 600 mg/kg body weight for 35 days. Blood glucose, glycosylated hemoglobin, triglyceride, LDL, VLDL, HDL, blood urea, cholesterol, number of β cells, and diameter of the islets of Langerhans were measured at the beginning and at the end of the experiment.Results:Blood glucose level and other parameters (except HDL) were elevated in the diabetic group, but were brought to control group level in the diabetic group treated with 600 mg/kg body weight of mulberry leaf extract. The diameter of the islets and the number of β cells were reduced in the diabetic group; both parameters were brought to control group level after treatment with mulberry leaf extract.Conclusion:Mulberry leaf extract, at a dose of 600 mg/kg body weight, has therapeutic effects in diabetes-induced Wistar rats and can restore the diminished β cell numbers.
Background: Chemotherapy agents can cause ovarian dysfunction and eventually lead to infertility. This study investigated the effect of nasturtium officinale extract on the ovarian function following the toxicity induced by doxorubicin in female rats. Methods: Forty eight female Wistar rats (180-210g) were randomly divided in six groups as follows: Group I, normal rats receiving 1ml normal saline; Group II and III receiving 25 and 75 mg/kg of the extract daily by gavage for 21 days. Groups IV, V and VI receiving 10 mg/kg doxorubicin intraperitoneally on the first day. In addition, Group IV and V received 25 and 75 mg/kg of the extract, respectively. The serum levels of estrogen, progesterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and ovarian Malondialdehyde (MDA) were determined after 21 days of treatment. The mean numbers of various graafian follicles and corpus lutea were recorded after treatment. Results: The mean serum FSH level in Group VI (0.11±0.01) significantly reduced compared to those in Groups II (0.21±0.05) and III (0.23±0.01), (P<0.05). The mean serum LH and estrogen levels in Group VI (0.16±0.08) reduced insignificantly compared to those in the controls (0.21±0.02), and in Groups II (0.23±0.03) and III (0.22±0.09). A significant reduction in the number of primary, secondary and graafian follicles were observed in Group VI compared to the control group (P<0.05). The serum MDA level significantly declined in Group V compared to that in Group VI (P<0.05). Conclusion: The nasturtium officinale extract attenuated the toxic effect of doxorubicin on the rat ovaries and protected the cell division in the follicles and the oocytes maturation.
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