Calcium Homeostasis in Ventricular Myocytes of Diabetic Cardiomyopathy

© 2020 Lina T. Al Kury. Diabetes mellitus (DM) is a chronic metabolic disorder commonly characterized by high blood glucose levels, resulting from defects in insulin production or insulin resistance, or both. DM is a leading cause of mortality and morbidity worldwide, with diabetic cardiomyopathy as one of its main complications. It is well established that cardiovascular complications are common in both types of diabetes. Electrical and mechanical problems, resulting in cardiac contractile dysfunction, are considered as the major complications present in diabetic hearts. Inevitably, disturbances in the mechanism(s) of Ca2+ signaling in diabetes have implications for cardiac myocyte contraction. Over the last decade, significant progress has been made in outlining the mechanisms responsible for the diminished cardiac contractile function in diabetes using different animal models of type I diabetes mellitus (TIDM) and type II diabetes mellitus (TIIDM). The aim of this review is to evaluate our current understanding of the disturbances of Ca2+ transport and the role of main cardiac proteins involved in Ca2+ homeostasis in the diabetic rat ventricular cardiomyocytes. Exploring the molecular mechanism(s) of altered Ca2+ signaling in diabetes will provide an insight for the identification of novel therapeutic approaches to improve the heart function in diabetic patients

Breast Cancer Awareness Among Zayed University Female Students

Background/Aim : Breast cancer is one of the most common cancers among female population worldwide. In the United Arab Emirates, breast cancer accounts for 31-43% of all cancer types. Recently, breast cancer incidence has declined as a result of development of better diagnostic techniques. Good knowledge and awareness about early detection of signs and symptoms of the disease are the most important keys for reducing morbidity and mortality. This study aims to evaluate the level of awareness about the risk factors of breast cancer, as well as, the knowledge about screening methods among female students at Zayed University in Abu Dhabi. Method: Â A random cross-sectional survey was carried to evaluate the level of awareness about breast cancer among female students at Zayed University. A total of 100 females aged 18 “31 from different colleges were included in the study. Data were analyzed using SPSS 21 program. Chi- square test was used together with Fisher\u27s exact test, as appropriate. P value \u3c0.05 was considered significant. Results: The results show that there is a lack of knowledge and awareness about the risk factors for breast cancer. Only 12% of the participants knew that physical inactivity is a risk factor. However, 29% of the participants knew that obesity is a risk factor. Knowledge about screening methods was poor and varied according to the marital and educational status of the students. Only 17% of the total participants have done breast self-examination. Single women had less frequently performed breast self-examination compared to married women Although 40% of the participants knew about ultra sound, only 22% of the students did have the knowledge about the proper age of mammogram screening. Conclusion: The results point to the lack of awareness among female students about breast cancer, the risk factors and screening methods. Therefore, effective educational programs are required to improve the knowledge level of university students regarding breast cancer and related practices

Breast Cancer Awareness Among Zayed University Female Students

Background/Aim: Breast cancer is one of the most common cancers among female population worldwide. In the United Arab Emirates, breast cancer accounts for 31-43% of all cancer types. Recently, breast cancer incidence has declined as a result of development of better diagnostic techniques. Good knowledge and awareness about early detection of signs and symptoms of the disease are the most important keys for reducing morbidity and mortality. This study aims to evaluate the level of awareness about the risk factors of breast cancer, as well as, the knowledge about screening methods among female students at Zayed University in Abu Dhabi. Method:  A random cross-sectional survey was carried to evaluate the level of awareness about breast cancer among female students at Zayed University. A total of 100 females aged 18–31 from different colleges were included in the study. Data were analyzed using SPSS 21 program. Chi- square test was used together with Fisher’s exact test, as appropriate. P value <0.05 was considered significant. Results: The results show that there is a lack of knowledge and awareness about the risk factors for breast cancer. Only 12% of the participants knew that physical inactivity is a risk factor. However, 29% of the participants knew that obesity is a risk factor. Knowledge about screening methods was poor and varied according to the marital and educational status of the students. Only 17% of the total participants have done breast self-examination. Single women had less frequently performed breast self-examination compared to married women Although 40% of the participants knew about ultra sound, only 22% of the students did have the knowledge about the proper age of mammogram screening. Conclusion: The results point to the lack of awareness among female students about breast cancer, the risk factors and screening methods. Therefore, effective educational programs are required to improve the knowledge level of university students regarding breast cancer and related practices

Immunomodulatory and anticancer activities of hyacinthus orientalis l.: An in vitro and in vivo study

Hyacinthus orientalis L. (family Hyacinthaceae) is traditionally used to treat different diseases including cancer. In this study, the anticancer and immunomodulatory effects of this plant were evaluated. Hydroalcoholic extract was prepared, and different solvent fractions were obtained using solvent–solvent extraction. In the anticancer part, MTT assay and caspase-3 ELISA kits were used to measure the antiproliferative and apoptosis induction ability for each extract, respectively. In the immunomodulatory part, lymphocyte proliferation assay and cytokines detection kit were used to measure the effect of extracts of acquired immunity. Phagocytosis and pinocytosis induction were used to evaluate the effect of extracts on the innate immunity. GC–MS, LC–MS, and Foline–Ciocalteu assays were used to identify the chemical composition of the plant. Balb/C mice were inoculated with breast cancer and treated with hydroalcoholic extract of H. orientalis L. Results showed that hydroalcoholic extract and n-hexane fraction were highly effective in apoptosis induction. Both extract and fraction were also effective in stimulating lymphocytes proliferation and phagocytosis. Significant reduction in tumor size was achieved after treating tumor-bearing mice with hydroalcoholic extract. Additionally, high cure percentages (50%) were obtained in treated mice. Results of this study showed that H. orientalis L. has promising anticancer and immunomodulatory activities. However, further studies are needed to explore more details of apoptosis induction ability and other mechanisms of action and to measure different signaling pathways responsible for the anticancer and immunomodulatory response

Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM

Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM

Xanthium spinosum L. Extracts Inhibit Breast Cancer in Mice by Apoptosis Induction and Immune System Modulation

Plants have been considered for many years as an important source of medicine to treat different diseases. Xanthium spinosum L. (Asteraceae, Compositae) is known for its diuretic, anti-inflammatory, and sedative effects. It is also used in the treatment of several ailments, such as cancer. In order to evaluate the anticancer and immunomodulatory activities, crude ethanol extract was prepared from the aerial part of X. spinosum and then fractionated using solvents with different polarities. As well, the chemical composition of X. spinosum extract and fractions were identified using LC-MS analysis. The antitumor effect of X. spinosum was assessed in both in vitro and in vivo models. Apoptosis induction was measured in vitro using a caspase-3 activity kit. Lymphocyte proliferation and phagocytosis and pinocytosis induction were used to quantify the effect of the plant extract and fractions on acquired and innate immunity, respectively. The effect of X. spinosum extract, and fractions on the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in murine lymphocytes was determined using a mouse-uncoated TH1/TH2 ELISA kit. Results showed that ethanol extract had the highest antiproliferative activity (IC₅₀ = 2.5 mg mL−1) against EMT6/P cell lines, while the aqueous and chloroform fractions had the highest apoptotic activity with 2.2 and 1.7 folds, respectively. On the other hand, the n-hexane fraction was the most effective in stimulating lymphocyte proliferation, whereas ethanol extract, aq. Methanol and aqueous fractions exhibited the highest phagocytic activity. As well, X. spinosum extract and fractions were able to modulate the expression of IL-2, IL-4, and IFN-γ. A remarkable decrease in tumor size was accomplished following the treatment of tumor-bearing mice with X. spinosum extract and fractions. Both aq. Methanol and chloroform fractions showed the highest percentage change in tumor size with -58 and -55%, respectively. As well, tumor-bearing mice treated with chloroform fraction demonstrated a high curable percentage with a value of 57.1%. Anyway, X. spinosum extract and fractions exhibited no toxic impact on the liver or kidney functions of the mice-treated groups. These findings may confirm that X. spinosum has favorable anticancer and immunomodulatory effects. However, additional studies are required to fully understand the mechanisms of action of this plant and the signaling pathways involved in its effects. Moreover, more testing is needed to have better insight into the apoptotic pathway and to know the exact concentration of active compounds

Resveratrol and tumor microenvironment: mechanistic basis and therapeutic targets

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Resveratrol (3,40,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tumor microenvironment. These players include blood and lymphatic vessels, infiltrating immune cells, stromal fibroblasts and the extracellular matrix. Targeting tumor microenvironment components is a promising strategy in cancer therapy. Resveratrol with its diverse biological activities has the capacity to target tumor microenvironment by manipulating the function of many components surrounding cancer cells. This review summarizes the targets of resveratrol in tumor microenvironment and the mechanisms involved in this targeting. Studies discussed in this review will participate in building a solid ground for researchers to have more insight into the mechanism of action of resveratrol in tumor microenvironment

Terfezia boudieri: A Desert Truffle With Anticancer and Immunomodulatory Activities

© Copyright © 2020 Al Obaydi, Hamed, Al Kury and Talib. Desert truffles have high nutritional value and grow wild in the Mediterranean basin and Western Asia. Although, many studies were performed to evaluate truffles nutritious values and phytochemical composition, studies are limited to evaluate their anticancer and/ or immunomodulatory effects. Our study was conducted to evaluate the anticancer and immunomodulatory effects of Terfezia boudieri (desert truffle). Different solvent extracts were prepared from the truffle and MTT assay was used to measure their anticancer activity against cancer cell lines (T47D, MCF-7, MDA-MB231, HCT-116, and Hela). Total phenolic content in each extract was determined by using Folin-Ciocalteu reagent and qualitative phytochemical screening was performed using standard methods. The degree of apoptosis induction (using caspase 3 assay) and vascular endothelial growth factor expression were detected using standard kits. Also, ELISA was used to measure levels of IFN-γ, IL-2, IL-4, and IL-10 secreted by splenocytes after treatment with the extracts. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay and pinocytosis function was evaluated using neutral red method. Terpenoids, phytosterols, and carbohydrates were present in all the solvent extracts, while tannins, alkaloids and flavonoids were detected only in aqueous/methanol and aqueous extracts. The highest total phenolic content was observed in aqueous and aqueous methanol extracts. The growth of cancer cell lines was inhibited by T. boudieri extracts in a dose dependent manner. N-hexane extract was the most potent against most cell lines. Aqueous/methanol extract showed high apoptosis induction and angiogenesis suppression effects. An increase in TH1 cytokines (IFN-γ, IL-2) level and a decrease in TH2 cytokine (IL-4) level were evident after lymphocytes stimulation by aqueous/methanol, n-hexane and ethyl acetate extracts of T. boudieri. Ethyl acetate extract of T. boudieri were the most potent extracts to stimulate lymphocytes proliferation while all other extracts showed moderate stimulation. Aqueous/methanol extract was the most active extract to stimulate phagocytosis. Ethyl acetate extract was the most active extract to stimulate pinocytosis. The use of T. boudieri provides variable health benefits. N-hexane, ethyl acetate, and aqueous/methanol extracts exhibited anticancer activities and are potent stimulators of innate and acquired immunity. Further testing is needed to identify the biologically active compounds and detect them quantitatively using GC-MS analysis