The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, we... more The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT 3 ) receptors expressed in Xenopus laevis oocytes. 5-HT (1 mM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC 50 5 163 mM) manner. The effects of menthol developed gradually, reaching a steadystate level within 10-15 minutes and did not involve G-proteins, since GTPgS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (2), (1), and racemic menthol inhibited 5-HT 3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(oaminophenoxy)ethane-N,N,N9,N9-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by incr...
IntroductionMajor depressive disorder (MDD) is a debilitating human health status characterized b... more IntroductionMajor depressive disorder (MDD) is a debilitating human health status characterized by mood swings and high suicidal attempts. Several studies have reported the role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression needs to be further investigated. The present study demonstrated the neuroprotective effects of Acetyl-L- carnitine (ALC) alone or in combination with caffeic acid phenethyl ester (CAPE) on lipopolysaccharide (LPS) induced neuro-inflammation, depression, and anxiety-like behavior.Material and methodsMale Sprague Dawley (SD) rats were used to explore the relative effects of ALC and the mechanistic interplay of the peroxisome proliferator-activated receptors (PPARγ) in depression. Lipopolysaccharide (LPS) was administered to induce depression and anxiety-like symptoms such as a decreased grooming tendency, diminished locomotive activity, and increased immobility period.ResultsWe found marked neur...
Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The... more Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)‐induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection.
Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physi... more Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mICAT), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mICAT, which is mainly carried by TRPC4 cation channels in ileal smooth mu...
Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible f... more Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base...
Ginkgo biloba extract possess several promising biological activities; currently, it is clinicall... more Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All ...
Resveratrol (3,4′,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has... more Resveratrol (3,4′,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 ...
Major depressive disorder (MDD) is a debilitating human health condition characterized by mood sw... more Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been wellinvestigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior. Methods: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression. Results: We found marked neuronal alterations in the cortex and hippocampus of LPSintoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings. Conclusion: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.
A better understanding of the negative impact of general anesthetics on gastrointestinal motility... more A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intes...
The release of reactive oxygen species (ROS) and oxidative stress is associated with the developm... more The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated f...
Diabetes mellitus (DM) is a chronic metabolic disorder commonly characterized by high blood gluco... more 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 under...
Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding ... more Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized ...
Background/Aim: Breast cancer is one of the most common cancers among female population worldwide... more 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....
Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorder... more Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR)...
Shah et al. Pathological Comparisons of t-MCAO and p-MCAO related signaling, synaptic transmissio... more Shah et al. Pathological Comparisons of t-MCAO and p-MCAO related signaling, synaptic transmission markers, neuron inflammatory and oxidative stress molecules. These differences may reflect the variations in different models, which may provide valuable information for mechanistic and therapeutic inconsistences as experienced in both preclinical models and clinical trials.
IntroductIon Diabetes mellitus (DM) is a global health problem. According to the International Di... more IntroductIon Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045 (http://www.diabetesatlas.org/resources/2017-atlas.html). Although DM can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. [1-3] Diabetic patients frequently suffer from systolic and diastolic dysfunction. [4-6] The streptozotocin (STZ)-induced diabetic rat is a widely used experimental model of DM. STZ causes damage to the pancreatic β-cells, which in turn leads to a reduction in insulin synthesis and release and a consequent rise in blood glucose. [7,8] Abnormalities in a variety of haemodynamic indices including stroke volume, ejection fraction, cardiac output, rate of pressure development and relaxation have been widely demonstrated in the STZ-induced diabetic heart. [9-12] At the level of the individual ventricular myocyte, many studies have demonstrated prolonged time course of contraction and relaxation [13,14] and either Introduction: Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045. Although diabetes can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. Diabetic patients frequently suffer from systolic and diastolic dysfunction. Within the ventricles, the electromechanical properties of cardiac myocytes vary transmurally. Aims and Objectives: The aim of this study was to investigate contraction and Ca 2+ transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle in the streptozotocin (STZ)-induced diabetic rat heart. Materials and Methods: Experiments were performed 5-6 months after STZ treatment. Ventricular myocytes were isolated by enzymic and mechanical dispersal techniques from EPI and ENDO regions of the left ventricle. Contraction and free intracellular Ca 2+ concentration [Ca 2+ ]i were measured by video edge detection and fluorescence photometry techniques, respectively. Results: Myocyte length and calculated surface area were smaller in EPI-STZ compared to EPI-CON. Time to peak (TPK) shortening was prolonged in EPI-STZ compared to EPI-CON and in ENDO-STZ compared to ENDO-CON myocytes. Time to half (THALF) relaxation of shortening was prolonged in EPI-STZ compared to EPI-CON. TPK Ca 2+ transient was prolonged in EPI-STZ compared to EPI-CON, ENDO-STZ compared to ENDO-CON, ENDO-STZ compared to EPI-STZ and in ENDO-CON compared to EPI-CON myocytes. THALF decay of the Ca 2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Fractional release of Ca 2+ was increased in ENDO-STZ compared to ENDO-CON and in ENDO-STZ compared to EPI-STZ. Recovery of the Ca 2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Conclusion: In conclusion the kinetics of contraction and Ca 2+ transient and fractional release of Ca 2+ from the sarcoplasmic reticulum are altered to different extents in EPI and ENDO myocytes from STZ-induced diabetic rat.
Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protect... more Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. Methods: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. Results: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol. Conclusion: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers.
Phil-Ok Koh was not included as an author in the published article. The corrected Author Contribu... more Phil-Ok Koh was not included as an author in the published article. The corrected Author Contributions Statement appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. AUTHOR CONTRIBUTIONS FA and GL managed the experimental work. FA and GL performed surgery, western blot, morphological experiments; performed data analysis. AZ,
The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, we... more The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT 3 ) receptors expressed in Xenopus laevis oocytes. 5-HT (1 mM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC 50 5 163 mM) manner. The effects of menthol developed gradually, reaching a steadystate level within 10-15 minutes and did not involve G-proteins, since GTPgS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (2), (1), and racemic menthol inhibited 5-HT 3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(oaminophenoxy)ethane-N,N,N9,N9-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by incr...
IntroductionMajor depressive disorder (MDD) is a debilitating human health status characterized b... more IntroductionMajor depressive disorder (MDD) is a debilitating human health status characterized by mood swings and high suicidal attempts. Several studies have reported the role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression needs to be further investigated. The present study demonstrated the neuroprotective effects of Acetyl-L- carnitine (ALC) alone or in combination with caffeic acid phenethyl ester (CAPE) on lipopolysaccharide (LPS) induced neuro-inflammation, depression, and anxiety-like behavior.Material and methodsMale Sprague Dawley (SD) rats were used to explore the relative effects of ALC and the mechanistic interplay of the peroxisome proliferator-activated receptors (PPARγ) in depression. Lipopolysaccharide (LPS) was administered to induce depression and anxiety-like symptoms such as a decreased grooming tendency, diminished locomotive activity, and increased immobility period.ResultsWe found marked neur...
Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The... more Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)‐induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection.
Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physi... more Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mICAT), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mICAT, which is mainly carried by TRPC4 cation channels in ileal smooth mu...
Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible f... more Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base...
Ginkgo biloba extract possess several promising biological activities; currently, it is clinicall... more Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All ...
Resveratrol (3,4′,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has... more Resveratrol (3,4′,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 ...
Major depressive disorder (MDD) is a debilitating human health condition characterized by mood sw... more Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been wellinvestigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior. Methods: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression. Results: We found marked neuronal alterations in the cortex and hippocampus of LPSintoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings. Conclusion: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.
A better understanding of the negative impact of general anesthetics on gastrointestinal motility... more A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intes...
The release of reactive oxygen species (ROS) and oxidative stress is associated with the developm... more The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated f...
Diabetes mellitus (DM) is a chronic metabolic disorder commonly characterized by high blood gluco... more 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 under...
Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding ... more Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized ...
Background/Aim: Breast cancer is one of the most common cancers among female population worldwide... more 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....
Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorder... more Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR)...
Shah et al. Pathological Comparisons of t-MCAO and p-MCAO related signaling, synaptic transmissio... more Shah et al. Pathological Comparisons of t-MCAO and p-MCAO related signaling, synaptic transmission markers, neuron inflammatory and oxidative stress molecules. These differences may reflect the variations in different models, which may provide valuable information for mechanistic and therapeutic inconsistences as experienced in both preclinical models and clinical trials.
IntroductIon Diabetes mellitus (DM) is a global health problem. According to the International Di... more IntroductIon Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045 (http://www.diabetesatlas.org/resources/2017-atlas.html). Although DM can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. [1-3] Diabetic patients frequently suffer from systolic and diastolic dysfunction. [4-6] The streptozotocin (STZ)-induced diabetic rat is a widely used experimental model of DM. STZ causes damage to the pancreatic β-cells, which in turn leads to a reduction in insulin synthesis and release and a consequent rise in blood glucose. [7,8] Abnormalities in a variety of haemodynamic indices including stroke volume, ejection fraction, cardiac output, rate of pressure development and relaxation have been widely demonstrated in the STZ-induced diabetic heart. [9-12] At the level of the individual ventricular myocyte, many studies have demonstrated prolonged time course of contraction and relaxation [13,14] and either Introduction: Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045. Although diabetes can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. Diabetic patients frequently suffer from systolic and diastolic dysfunction. Within the ventricles, the electromechanical properties of cardiac myocytes vary transmurally. Aims and Objectives: The aim of this study was to investigate contraction and Ca 2+ transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle in the streptozotocin (STZ)-induced diabetic rat heart. Materials and Methods: Experiments were performed 5-6 months after STZ treatment. Ventricular myocytes were isolated by enzymic and mechanical dispersal techniques from EPI and ENDO regions of the left ventricle. Contraction and free intracellular Ca 2+ concentration [Ca 2+ ]i were measured by video edge detection and fluorescence photometry techniques, respectively. Results: Myocyte length and calculated surface area were smaller in EPI-STZ compared to EPI-CON. Time to peak (TPK) shortening was prolonged in EPI-STZ compared to EPI-CON and in ENDO-STZ compared to ENDO-CON myocytes. Time to half (THALF) relaxation of shortening was prolonged in EPI-STZ compared to EPI-CON. TPK Ca 2+ transient was prolonged in EPI-STZ compared to EPI-CON, ENDO-STZ compared to ENDO-CON, ENDO-STZ compared to EPI-STZ and in ENDO-CON compared to EPI-CON myocytes. THALF decay of the Ca 2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Fractional release of Ca 2+ was increased in ENDO-STZ compared to ENDO-CON and in ENDO-STZ compared to EPI-STZ. Recovery of the Ca 2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Conclusion: In conclusion the kinetics of contraction and Ca 2+ transient and fractional release of Ca 2+ from the sarcoplasmic reticulum are altered to different extents in EPI and ENDO myocytes from STZ-induced diabetic rat.
Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protect... more Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. Methods: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. Results: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol. Conclusion: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers.
Phil-Ok Koh was not included as an author in the published article. The corrected Author Contribu... more Phil-Ok Koh was not included as an author in the published article. The corrected Author Contributions Statement appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. AUTHOR CONTRIBUTIONS FA and GL managed the experimental work. FA and GL performed surgery, western blot, morphological experiments; performed data analysis. AZ,
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Papers by Lina Kury