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1.
Cutan Ocul Toxicol ; 40(3): 241-251, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34056995

ABSTRACT

OBJECTIVE: To elucidate the implications of L-carnosine on interleukin-1α (IL-1α)-induced inflammation of lacrimal glands (LGs). MATERIALS AND METHODS: Forty rabbits were divided equally into four groups: control group (G1), IL-1α (G2), L-carnosine (G3), and L-carnosine plus IL-1α (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED). RESULTS: The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-γ, tumor necrosis factor-α, transforming growth factor-ß1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1α-induced inflammation of LGs. CONCLUSIONS: IL-1α induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED.HighlightsIL-1α induced dry eye disease through its oxidative stress, proinflammatory, apoptotic and profibrotic effects on the lacrimal glands of rabbit.L-carnosine has antioxidant, anti-inflammatory, antiapoptotic and antifibrotic effects.L-carnosine mitigated IL-1α induced dry eye disease via elevating the levels of FasL, IFN-γ, TNF-α, TGFß1 and MDA as well as reducing the levels of antioxidants (GPx, SOD, and catalase) and ROS in the lacrimal glands of rabbit.L-carnosine could be used as a novel adjuvant therapy for the treatment of dry eye disease.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Carnosine/pharmacology , Dry Eye Syndromes/drug therapy , Interleukin-1alpha/immunology , Animals , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Apoptosis/drug effects , Apoptosis/immunology , Carnosine/therapeutic use , Disease Models, Animal , Dry Eye Syndromes/immunology , Dry Eye Syndromes/pathology , Humans , Interleukin-1alpha/administration & dosage , Lacrimal Apparatus/drug effects , Lacrimal Apparatus/immunology , Lacrimal Apparatus/pathology , Male , Oxidative Stress/drug effects , Rabbits , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology
2.
Int J Nanomedicine ; 15: 5575-5589, 2020.
Article in English | MEDLINE | ID: mdl-32801705

ABSTRACT

PURPOSE: The overexpression of Her-2 in 25-30% breast cancer cases and the crosstalk between Her-2 and fatty acid synthase (FASN) establishes Her-2 as a promising target for site-directed delivery. The present study aimed to develop the novel lipid base formulations to target and inhibit the cellular proliferation of Her-2-expressing breast cancer cells through the silencing of FASN. In order to achieve this goal, we prepared DSPC/Chol and DOPE/CHEMS immunoliposomes, conjugated with the anti-Her-2 fab' and encapsulated FASN siRNA against breast cancer cells. METHODS: We evaluated the size, stability, cellular uptake and internalization of various formulations of liposomes. The antiproliferative gene silencing potential was investigated by the cell cytotoxicity, crystal violet, wound healing and Western blot analyses in Her-2+ and Her-2¯ breast cancer cells. RESULTS: The data revealed that both nanosized FASN-siRNA-encapsulated liposomes showed significantly higher cellular uptake and internalization with enhanced stability. The cell viability of Her-2+ SK-BR3 cells treated with the targeted formulation of DSPC/Chol- and DOPE/CHEMS-encapsulating FASN-siRNA reduced to 30% and 20%, respectively, whereas it was found to be 45% and 36% in MCF-7 cells. The wounds were not only failed to close but they became broader in Her-2+ cells treated with targeted liposomes of siRNA. Consequently, the amount of FASN decreased by 80% in SK-BR3 cells treated with non-targeted liposomes and it was 30% and 60% in the MCF-7 cells treated with DSPC/Chol and DOPE/CHEMS liposomes, respectively. CONCLUSION: In this study, we developed the formulation that targeted Her-2 for the suppression of FASN and, therefore, inhibited the proliferation of breast cancer cells.


Subject(s)
Breast Neoplasms/genetics , Fatty Acid Synthase, Type I/genetics , Molecular Targeted Therapy/methods , Receptor, ErbB-2/metabolism , Breast Neoplasms/therapy , Cell Line, Tumor , Cell Survival/genetics , Female , Gene Silencing , Humans , Hydrogen-Ion Concentration , Immunoglobulin Fab Fragments/chemistry , Lipids/chemistry , Liposomes/administration & dosage , Liposomes/chemistry , Liposomes/immunology , MCF-7 Cells , RNA, Small Interfering/genetics , Receptor, ErbB-2/immunology
3.
Asian Pac J Cancer Prev ; 20(4): 1153-1160, 2019 Apr 29.
Article in English | MEDLINE | ID: mdl-31030489

ABSTRACT

Objective: Cancer chemotherapy at the recommended doses is largely associated with toxicity, and also it is not effective enough to reduce the advancement of the disease at lower doses. Thymoquinone (TQ) is an active compound derived from black seeds (Nigella sativa) which exhibits anticancer activities. The aim of the present study was to investigate the synergistic effect of TQ alone and in combination with cyclophosphamide (cyclo), and to unravel the role of TQ in fatty acid synthase (FASN) mediated molecular signaling in Her2 + and Her2- breast cancer cell lines. Methods: The effect of TQ on the growth of Her2+ SKBR-3 and Her2- MDA-231 breast cancer lines were evaluated as percent cell viability by cytotoxicity-based MTT assay. The analysis of cell cycle arrest was done through flowcytometry followed by Western blot and RT-PCR to detect signaling events in the cells. Results: The data showed that TQ-cyclo (0.5mM-10µM) combination significantly inhibited the proliferation through the 5.49% and 57.72% accumulation of cells in sub-G1 and G1 respectively as 12% cells were shifted from G2/M phase in Her2+ breast cancer cells. Similarly, TQ-cyclo (0.5mM-20µM) combination exhibited that the 16.6% cells were arrested in Sub-G1 and only 3.54% cells were remained in G2/M phase as it was 22.89% in DMSO control in Her-2- breast cancers cells. Though TQ alone or in combination with cyclo alleviated the PI3K/Akt signaling by downregulating the phosphorylation of Akt and upregulating the PTEN, no changes was observed in FASN and Her-2 as well in both type of cells. The significant decreased expression of cyclin D1 was found in TQ-cyclo combinations. Conclusion: The current findings suggested that TQ can alter the cell cycle progression and induce cell death independent of FASN mediated signaling. In terms of clinical perspective, the present study clearly showed that TQ can broadly augment the effect of cyclo in breast cancer cases irrespective of Her-2+ or Her-.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Benzoquinones/pharmacology , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cyclophosphamide/pharmacology , Drug Synergism , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Cycle/drug effects , Female , Humans , Signal Transduction/drug effects , Tumor Cells, Cultured
4.
PLoS One ; 13(12): e0208951, 2018.
Article in English | MEDLINE | ID: mdl-30589842

ABSTRACT

The present study was aimed to develop a liposomal formulation of thymoquinone (Lip-TQ) to treat Candida albicans infection in diabetic mice. Streptozotocin (STZ) was injected to induce hyperglycemia and on day 3 post STZ administration, mice were intravenously infected with C. albicans. Various doses (2, 5 and 10 mg/kg) of Free or Lip-TQ were administered in C. albicans infected diabetic mice. The effect of Lip-TQ was also determined on the organ indices, liver and kidney function parameters. Lip-TQ at a dose of 10 mg/kg significantly reduced the level of the blood glucose and alleviated the systemic C. albicans infection in diabetic mice. C. albicans infected diabetic mice treated with Lip-TQ at a dose of 10 mg/kg showed the survival rate of 70% as compared to that of 20% in the group treated with free TQ. The treatment with Lip-TQ resulted in the recovery of the organ indices, liver inflammation, kidney functioning and pancreas regeneration in diabetic mice. Moreover, TQ formulations also showed the direct therapeutic effect against candidiasis in the untreated or metformin-treated diabetic mice. Therefore, the findings of the present study support the use of Lip-TQ in the treatment of candidiasis in the diabetic patients.


Subject(s)
Benzoquinones/administration & dosage , Candidiasis/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Liposomes/administration & dosage , Animals , Benzoquinones/chemistry , Blood Glucose , Candida albicans/drug effects , Candida albicans/pathogenicity , Candidiasis/complications , Candidiasis/microbiology , Candidiasis/pathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/microbiology , Diabetes Mellitus, Experimental/physiopathology , Disease Models, Animal , Humans , Liposomes/chemistry , Liver/drug effects , Liver/microbiology , Mice
5.
Adv Biomed Res ; 7: 38, 2018.
Article in English | MEDLINE | ID: mdl-29629341

ABSTRACT

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases.

6.
J Drug Target ; 26(8): 709-719, 2018 09.
Article in English | MEDLINE | ID: mdl-29307241

ABSTRACT

Natural Killer T (NKT) cells play an important role in host's anti-tumour immune response. Glycosphingolipids (GSLs) isolated from Sphingomonas paucimobilis have the ability to stimulate NKT cells. In this study, the activity of free GSLs or GSLs-incorporated liposomes (glycosphingosomes) was investigated against dimethyl-α-benzanthracene (DMBA)-induced tumours in mice. The anti-tumour immunity of GSLs- or glycosphingosomes-loaded bone marrow-derived dendritic cells (BMDCs) was investigated in tumour-bearing mice. The Immunotherapeutic potential of co-administration of liposomal doxorubicin (Lip-Dox) and GSLs or glycosphingosomes was assessed by measuring cytokine levels and VEGF in the tumour tissues. Pretreatment with glycosphingosomes significantly delayed the frequency of tumour formation. Immunotherapy with glycosphingosomes-loaded BMDCs increased serum IFN-γ level and survival rate in mice. The effect of immunotherapy was dependent on effector functions of NK cells because the depletion of NK cells abolished the effects of immunotherapy. There was reduced tumour growth with low expression of VEGF in the group of mice treated with glycosphingosomes and Lip-Dox combination. Moreover, the splenocytes secreted higher levels of IFN-γ, IL-12 and lower TGF-ß level. The results of this study indicate that glycosphingosomes can induce better antitumour immunity and may be considered a novel formulation in antitumour therapy.


Subject(s)
Glycosphingolipids/physiology , Liposomes , Neoplasms, Experimental/immunology , Sphingomonas/immunology , Animals , Female , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology
7.
Curr Diabetes Rev ; 14(6): 523-533, 2018.
Article in English | MEDLINE | ID: mdl-28914194

ABSTRACT

BACKGROUND: Diabetic Retinopathy is a leading cause of sight-threatening complication, which occurs due to a number of physiological and metabolic abnormalities during later stages of diabetes. Many of these abnormal changes are consistent with altered oxidative stress, inflammation, genetic set up, advanced glycation end products, and hematological changes. So the altered levels of different biomolecules related to these changes serve as important biomarkers to assess better evaluation and early treatment of this disease. Some treatments like laser therapy may be fast and specific but are more expensive, limited and can result in severe contraindications. Several other novel treatment strategies have been evolved recently besides classical approaches like control over hyperglycemia, hypertension, lipid profile to control diabetic retinopathy. These precise treatments are based on targeting the elevated biomarkers in retina. Such treatments include use of anti-VEGF therapy, intravitreal corticosteroids, gamigliptin and flavonoids. CONCLUSION: The present review discusses the latest updates on diabetic retinopathy, common etiology, different biomarkers and current treatments. In conclusion, perfection and proper supervision of diabetes and early treatment of diabetic retinopathy are crucial in controlling the occurrence and severity of this disease.


Subject(s)
Biomarkers , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/therapy , Angiogenesis Inhibitors/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Humans , Laser Therapy , Retina/physiopathology
8.
J Ethnopharmacol ; 195: 159-165, 2017 Jan 04.
Article in English | MEDLINE | ID: mdl-27825990

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The development of compounds able to improve metabolic syndrome and mitigate complications caused by inappropriate glycemic control in type 1 diabetes mellitus is challenging. The medicinal plant with established hypoglycemic properties Garcinia kola Heckel might have the potential to mitigate diabetes mellitus metabolic syndrome and complications. AIM OF THE STUDY: We have investigated the neuroprotective properties of a suspension of G. kola seeds in long-term type 1 diabetes mellitus rat model. MATERIALS AND METHODS: Wistar rats, made diabetic by single injection of streptozotocin were monitored for 8 months. Then, they were administered with distilled water or G. kola oral aqueous suspension daily for 30 days. Body weight and glycemia were determined before and after treatment. After sacrifice, cerebella were dissected out and processed for stereological quantification of Purkinje cells. Histopathological and immunohistochemical analyses of markers of neuroinflammation and neurodegeneration were performed. RESULTS: Purkinje cell counts were significantly increased, and histopathological signs of apoptosis and neuroinflammation decreased, in diabetic animals treated with G. kola compared to diabetic rats given distilled water. Glycemia was also markedly improved and body weight restored to non-diabetic control values, following G. kola treatment. CONCLUSIONS: These results suggest that G. kola treatment improved the general condition of long-term diabetic rats and protected Purkinje cells partly by improving the systemic glycemia and mitigating neuroinflammation.


Subject(s)
Cerebellar Diseases/prevention & control , Cerebellum/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetic Neuropathies/prevention & control , Garcinia kola/chemistry , Hypoglycemic Agents/pharmacology , Nerve Degeneration , Neuroprotective Agents/pharmacology , Plant Preparations/pharmacology , Animals , Apoptosis/drug effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Cerebellar Diseases/blood , Cerebellar Diseases/etiology , Cerebellar Diseases/pathology , Cerebellum/metabolism , Cerebellum/pathology , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/chemically induced , Diabetic Neuropathies/blood , Diabetic Neuropathies/etiology , Diabetic Neuropathies/pathology , Hypoglycemic Agents/isolation & purification , Neuroimmunomodulation/drug effects , Neuroprotective Agents/isolation & purification , Phytotherapy , Plant Preparations/isolation & purification , Plants, Medicinal , Purkinje Cells/drug effects , Purkinje Cells/metabolism , Purkinje Cells/pathology , Rats, Wistar , Streptozocin , Time Factors , Tumor Necrosis Factor-alpha/metabolism , fas Receptor/metabolism
9.
Int J Nanomedicine ; 10: 6331-8, 2015.
Article in English | MEDLINE | ID: mdl-26504383

ABSTRACT

The present study aimed to assess the antitumor effect of glycosphingolipid-incorporated liposomes (glycosphingosomes) in combination with liposomal doxorubicin (Lip-Dox) in a mouse model of fibrosarcoma. Glycosphingosomes were prepared by incorporating glycosphingolipids isolated from Sphingomonas paucimobilis into the liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, and cardiolipin. Tumors were induced by administering dimethyl-α-benzanthracene, and tumor-bearing mice were treated with various formulations of Dox, including free Dox, Lip-Dox, or glycosphingosomes + Lip-Dox. Mice were observed for 90 days to monitor their survival and tumor size. Free Dox, but not Lip-Dox or a combination of glycosphingosomes and Lip-Dox, caused the substantial depletion of leukocytes and significantly increased the levels of lactate dehydrogenase and creatinine kinase in mice. Tumor-bearing mice treated with a combination of glycosphingosomes and Lip-Dox showed restricted tumor growth and increased survival when compared to those treated with free Dox or Lip-Dox. The results of the present study suggest that a combination of glycosphingosomes and Lip-Dox may prove to be very effective in the treatment of tumors.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Doxorubicin/analogs & derivatives , Fibrosarcoma/chemically induced , Fibrosarcoma/drug therapy , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Animals , Cell Proliferation/drug effects , Chemistry, Pharmaceutical , Doxorubicin/chemistry , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Female , Fibrosarcoma/pathology , Mice , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Polyethylene Glycols/therapeutic use , Survival Analysis
10.
Pharmacogn Rev ; 9(18): 120-6, 2015.
Article in English | MEDLINE | ID: mdl-26392709

ABSTRACT

Treatment based on natural products is rapidly increasing worldwide due to the affordability and fewer side effects of such treatment. Various plants and the products derived from them are commonly used in primary health treatment, and they play a pivotal role in the treatment of diseases via modulation of biochemical and molecular pathways. Aloe vera, a succulent species, produces gel and latex, plays a therapeutic role in health management through antioxidant, antitumor, and anti-inflammatory activities, and also offers a suitable alternative approach for the treatment of various types of diseases. In this review, we summarize the possible mechanism of action and the therapeutic implications of Aloe vera in health maintenance based on its modulation of various biological activities.

11.
Middle East Afr J Ophthalmol ; 22(1): 86-91, 2015.
Article in English | MEDLINE | ID: mdl-25624680

ABSTRACT

PURPOSE: To determine the prevalence and causes of amblyopia in primary school children in Qassim province, Kingdom of Saudi Arabia (KSA). MATERIALS AND METHODS: In this cross sectional study, 5176 children, aged 6 to 13 years (mean - 9.53 ± 1.88 years) were evaluated. There were 2573 (49.71%) males and 2603 (50.29%) females. Distance visual acuity (V/A) was tested monocularly using a logMAR chart with and without correction. Cycloplegic refraction was performed in children with reduced vision. To determine the etiology of amblyopia, children were enrolled if there was a difference in V/A of two or more lines between eyes or an absolute reduction in acuity <20/30 in either eye, that could not be corrected by refraction. P ≤ 0.05 was considered statistically significant. RESULTS: There 202 out of 5176 (3.90%) with ambylopia. There are 98 (1.88%) amblyopic females. There was no statistical difference in gender for amblyopes (P > 0.05). The prevalence of amblyopia was statistically significant higher in the older age group (10-13 year) compared to younger age group (6 to 9 years) (P < 0.05). Unilateral amblyopia (3.24%) was more frequent than bilateral amblyopia (0.66%). The most frequent causes of amblyopia were refractive error (94.56%), of which anisometropic amblyopia was present in 77.72%, isoametropic amblyopia in 16.84% and strabismus in 5.44%. CONCLUSION: The prevalence of amblyopia in Qassim province, KSA, is 3.9% which is similar or higher than other published studies on amblyopia. Anisometropic refractive errors are the most common underlying cause for this population. We recommend implementation of visual screening programs for children with appropriate clinical and social settings for early detection and proper management of amblyopia.


Subject(s)
Amblyopia/epidemiology , Adolescent , Amblyopia/diagnosis , Amblyopia/etiology , Child , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Refractive Errors/epidemiology , Risk Factors , Saudi Arabia/epidemiology , Vision Screening
12.
Int J Health Sci (Qassim) ; 8(3): 257-67, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25505861

ABSTRACT

AIM: This study aimed to investigate the pathogenic effect of bacteria causing infectious keratitis among patients through experimental study conducted on rabbits' eyes with the aid of histopathology as eye infection is a common disease in developing countries that may complicate to loss of vision. METHODOLOGY: 100 swab samples were collected from human infected eyes, at Qassim region during 2012, for the isolation of Pseudomonas aeruginosa and Staphylococcus aureus. The isolated pathogenic bacteria were tested to various antibiotics using some selected antibiotics discs through agar-well diffusion method. Then, experimental study conducted on 27 rabbits. The rabbits were divided randomly into three equal groups, each containing 9 rabbits. Rabbits of group (1) served as control group (Negative Control) and their eyes were inoculated with the buffer only. Rabbits of group (2) were inoculated through eyes with the isolated Pseudomonas aeruginosa. Rabbits of group (3) were inoculated through eyes with the isolated Staphylococcus aureus. RESULTS: Out of 100 collected swab samples from human infected eyes, Pseudomonas aeruginosa and Staphylococcus aureus were isolated with a total percentage of 25.21% and 15.65%; respectively and used in this study. Both bacterial isolates were sensitive to Gentamicin and Cefuroxime. Clinically, experimentally infected rabbits by Pseudomonas aeruginosa, revealed varying degree corneal abrasions, corneal abscess and dense corneal opacity. Histopathologically, at 3(rd) day post-infection (PI), the cornea revealed polymorpho-nuclear cells infiltration with loss of the outer epithelial lining. At 7(th) day PI, neutrophils were seen in the stroma. At 15(th) day PI, proliferation of fibroblasts and new vascularisation were seen in the stroma. Clinically, rabbits experimentally infected with Staphylococcus aureus, revealed corneal ulcers and focal abscesses. Histopathologically, at 3(rd) and 7(th) day PI, the cornea revealed edema and infiltration of leukocytes. At 15(th) day PI, hyperplasia of corneal epithelium and proliferation of keratocytes were evident. The liver and kidneys of experimented rabbits revealed no remarkable histopathological alterations along the period of experiment. CONCLUSION: Pseudomonas aeruginosa and Staphylococcus aureus are common eye infection in human, both induced severe lesions in the eyes of rabbits that could interfere with vision, therefore, strict measures to control these infections in human is recommended.

13.
Cancer Epidemiol ; 38(6): 765-72, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25448084

ABSTRACT

In breast cancer cells, overexpression of human epidermal growth factor receptor 2 (HER2) increases the translation of fatty acid synthase (FASN) by altering the activity of PI3K/Akt signaling pathways. Cancer chemotherapy causes major side effects and is not effective enough in slowing down the progression of the disease. Earlier studies showed a role for resveratrol in the inhibition of FASN, but the molecular mechanisms of resveratrol-induced inhibition are not known. In the present study, we examined the novel mechanism of resveratrol on Her2-overexpressed breast cancer cells. The effect of resveratrol on the growth of breast cancer cells was assessed as percent cell viability by cytotoxicity-based MTT assay and the induction of apoptosis was determined by cell-death detection ELISA and flow cytometric analysis of Annexin-V-PI binding. Western immunobloting was used to detect signaling events in human breast cancer (SKBR-3) cells. Data showed that resveratrol-mediated down-regulation of FASN and HER2 genes synergistically induced apoptotic death in SKBR-3 cells. This concurrently caused a prominent up-regulation of PEA3, leads to down-regulation of HER2 genes. Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression. These findings suggest that resveratrol alters the cell cycle progression and induce cell death via FASN inhibition in HER2 positive breast cancer.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Stilbenes/therapeutic use , Anticarcinogenic Agents/administration & dosage , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Female , Humans , Resveratrol , Signal Transduction , Stilbenes/administration & dosage
14.
Glob J Health Sci ; 6(5): 87-98, 2014 May 13.
Article in English | MEDLINE | ID: mdl-25168993

ABSTRACT

Peroxidases represent a family of isoenzymes actively involved in oxidizing reactive oxygen species, innate immunity, hormone biosynthesis and pathogenesis of several diseases. Different types of peroxidases have organ, tissues, cellular and sub-cellular level of specificities in their function. Different diseases lead to varied expressions of peroxidases based on several mechanisms proposed. Several researches are going on to understand its deficiency, over-expression and malfunction in relation with different diseases. Some common diseases of mankind like cancer, cardiovascular diseases and diabetes directly or indirectly involve the role of peroxidases. So the status of peroxidase levels may also function as a marker of different diseases. Although many types of diseases in human beings have a strong correlation with tissue specific peroxidases, the clear role of these oxido-reductases is not yet fully understood. Here we are focusing on the role of peroxidases in relations with different diseases occurring due to oxidative stress.


Subject(s)
Oxidative Stress/physiology , Peroxidases/metabolism , Reactive Oxygen Species/metabolism , Humans , Oxidative Stress/immunology
15.
J Optom ; 7(3): 168-76, 2014.
Article in English | MEDLINE | ID: mdl-25000873

ABSTRACT

PURPOSE: The worldwide prevalence of refractive errors (RE), which is a common cause of treatable visual impairment among children, varies widely. We assessed the prevalence of correctable visual impairment (uncorrected RE) in primary school children in Qassim, Saudi Arabia. METHODS: A cross-sectional study was conducted in 21 primary schools. A total of 5176 children (mean age 9.5±1.8 years), 2573 boys (49.7%) and 2603 girls (50.3%), underwent a comprehensive eye examination. The examinations consisted of visual acuity, autorefraction, cover test, ocular motility, pupillary evaluation, anterior segment examination, cycloplegic auto-refraction and dilated fundus examination with direct ophthalmoscopy. The children were divided into groups based on their age and gender. RESULTS: The overall prevalence of RE in the better eye was 18.6% (n=963), and the prevalence of uncorrected RE 16.3% (n=846), with only 2.3% (n=127) of children wearing spectacles during examination. The prevalence of uncorrected myopia (5.8%) and myopic astigmatism (5.4%) was higher compared to that of hyperopic astigmatism (2.7%), mixed astigmatism (1.7%) and hyperopia (0.7%). The anisometropia prevalence was 3.6%. Risks for astigmatism, myopia and anisometropia were positively associated with age. In addition, myopia and anisometropia risks were also associated with female gender, while risk of astigmatism was correlated with male gender. Few children with vision reducing RE wore spectacles; an additional 16.3% of children could benefit from spectacle prescription. CONCLUSION: The prevalence of uncorrected RE in children is relatively high and represents an important public health problem in school-aged children in Qassim province. Performance of routine periodical vision screening throughout childhood may reverse this situation.


Subject(s)
Refractive Errors/epidemiology , Adolescent , Age Distribution , Child , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Saudi Arabia/epidemiology , Sex Factors , Visual Acuity
16.
Cell Signal ; 26(4): 673-82, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24378534

ABSTRACT

Fate determination of neural crest cells is an essential step for the development of different crest cell derivatives. Peripheral glia development is marked by the choice of the neural crest cells to differentiate along glial lineages. The molecular mechanism underlying fate acquisition is poorly understood. However, recent advances have identified different transcription factors and genes required for the complex instructive signaling process that comprise both local environmental and cell intrinsic cues. Among others, at least the roles of Sox10, Notch, and neuregulin 1 have been documented in both in vivo and in vitro models. Cooperative interactions of such factors appear to be necessary for the switch from multipotent neural crest cells to glial lineage precursors in the peripheral nervous system. This review summarizes recent advances in the understanding of fate determination of neural crest cells into different glia subtypes, together with the potential implications in regenerative medicine.


Subject(s)
Neural Crest/metabolism , Neuroglia/metabolism , Peripheral Nervous System/metabolism , Signal Transduction , Animals , Cell Differentiation , Neural Crest/cytology , Neuregulin-1/metabolism , Neuroglia/cytology , Receptors, Notch/metabolism , SOXE Transcription Factors/metabolism , Stem Cells/cytology , Stem Cells/metabolism
17.
Saudi Med J ; 34(11): 1156-60, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24252894

ABSTRACT

OBJECTIVE: To study the incidence and risk factors of the bacteria causing infectious keratitis among patients in Qassim province of Saudi Arabia. METHODS: This is a cross sectional study conducted at the Department of Optometry, College of Applied Medical Sciences, Qassim University, Qassim, Kingdom of Saudi Arabia from December 2010 to May 2011. One hundred patients suspected of keratitis were subjected to clinical examinations. A total of 115 corneal swabs from these cases were collected under aseptic conditions for bacteriological examinations. RESULTS: Culture of the corneal swabs revealed Pseudomonas aeruginosa (25.2%), Staphylococcus aureus (15.7%), and unclassified bacteria (13.9%). However, 52 swabs of infectious keratitis cases (45.2%) were negative to bacteria. Contact lens wearing (44.4%) was the most common risk factor among the examined patients, followed by corneal trauma (21.7%), ocular surface disease (11.3%), and corneal surgery (7%). No significant correlation was observed between systemic risk factor and clinical presentation. CONCLUSION: It could be concluded that infectious keratitis was mostly due to Pseudomonas aeruginosa and Staphylococcus aureus. Therefore, strict measures are recommended to control and treat infectious keratitis to avoid visual complications.


Subject(s)
Bacterial Infections/epidemiology , Keratitis/epidemiology , Bacterial Infections/microbiology , Cross-Sectional Studies , Humans , Incidence , Keratitis/microbiology , Risk Factors
18.
J Clin Diagn Res ; 7(6): 1105-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23905114

ABSTRACT

BACKGROUND: Computer-based training (CBT) and internet-based training (IBT) have become a vital part of the Medical Education. A cross-sectional study was carried out in Qassim University-Kingdom of Saudi Arabia (KSA), with the objective of assessing the pattern of the computer and Internet utilization among both male and female medical students. METHODS: A total of 500 medical students from 4 different medical colleges of Qassim University participated in this study. A semi-structured, pre-tested questionnaire was used to collect the data and the data analysis was done by using SPSS, Version 17. RESULTS: Forty two percent female and twenty four percent male students used computers to get general information, 80% of the students reported using computers for academic activities and 52% females and 22% males used computers for entertainment. Most of the females preferred using computers at home (84%), while 54% males used computers at cyber cafés. For the information retrieval, 84% males used the internet, followed by journals/library (36%) and textbooks (35%), while the females preferred textbooks (75%) and the internet (14%). Google was found to be most commonly used search engine. CONCLUSION: The internet creates an educational delivery system; it is highly needed to increase the credit hours for the university requirement courses in computer application and the internet use for both among the male and female students.

19.
Malar J ; 12: 298, 2013 Aug 29.
Article in English | MEDLINE | ID: mdl-23984986

ABSTRACT

BACKGROUND: Cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite Plasmodium falciparum. Drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. The potential of the medicinal plant Azadirachta indica (Neem) for the treatment of experimental cerebral malaria was evaluated in mice. METHODS: Experimental cerebral malaria was induced in mice by infection with Plasmodium berghei ANKA. Infected mice were administered with Azadirachta indica ethanolic extract at doses of 300, 500, or 1000 mg/kg intraperitoneally (i.p.) in experimental groups, or with the anti-malarial drugs chloroquine (12 mg/kg, i.p.) or artemether (1.6 mg/kg, i.p.), in the positive control groups. Treatment was initiated at the onset of signs of brain involvement and pursued for five days on a daily basis. Mice brains were dissected out and processed for the study of the effects of the extract on pyramidal cells' fate and on markers of neuroinflammation and apoptosis, in the medial temporal lobe. RESULTS: Azadirachta indica ethanolic extract mitigated neuroinflammation, decreased the severity of brain oedema, and protected pyramidal neurons from apoptosis, particularly at the highest dose used, comparable to chloroquine and artemether. CONCLUSIONS: The present findings suggest that Azadirachta indica ethanolic extract has protective effects on neuronal populations in the inflamed central nervous system, and justify at least in part its use in African and Asian folk medicine and practices.


Subject(s)
Antimalarials/administration & dosage , Apoptosis , Azadirachta/chemistry , Brain Edema/prevention & control , Malaria, Cerebral/drug therapy , Neurons/physiology , Plant Extracts/administration & dosage , Animals , Antimalarials/isolation & purification , Antimalarials/pharmacology , Brain/pathology , Brain Edema/pathology , Disease Models, Animal , Histocytochemistry , Injections, Intraperitoneal , Malaria, Cerebral/parasitology , Malaria, Cerebral/pathology , Malaria, Falciparum , Male , Mice , Neurons/drug effects , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plasmodium berghei/growth & development , Treatment Outcome
20.
Saudi Med J ; 34(6): 616-22, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23756927

ABSTRACT

OBJECTIVES: To assess lipid profile and lipid peroxidation in type 2 diabetics with proliferative retinopathy (PDR), and investigate the association between these biochemical parameters and PDR. METHODS: This study was conducted between June 2011 and February 2012 in the Research Laboratory, College of Applied Medical Sciences, Qassim University, Qasssim, Kingdom of Saudi Arabia. The study included 54 patients with type 2 diabetes (21 with PDR and 33 controls) and 30 healthy subjects. The biochemical parameters were measured using standard laboratory procedures. RESULTS: Patients with PDR characterized by significantly (p<0.05) increased levels of serum cholesterol, triglyceride, low density lipoprotein (LDL-C), plasma malondialdehyde; decreased levels of serum high density lipoprotein (HDL-C) and apolipoprotein A1 (Apo A1); positive correlation of malondialdehyde with triglyceride, but negative with HDL-C, Apo A1. In logistic regression, malondialdehyde, LDL-C, and Apo A1 were not associated with PDR. However, triglyceride (OR = 1.745; p=0.000), total cholesterol (OR = 0.079; p=0.000), and HDL-C (OR = 10.676; p=0.000) were independent risk factors for developing PDR. CONCLUSION: Dyslipidemia and lipid peroxidation may play a role in pathogenesis of diabetic retinopathy. Patients with PDR displayed marked lipid abnormalities and increased lipid peroxidation. The control of lipid alterations through glycemic control and/or lipid lowering medication is required for type 2 diabetics at least to postpone or prevent loss of vision from retinopathy.


Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/complications , Dyslipidemias/complications , Lipid Peroxidation , Aged , Blood Glucose/analysis , Cholesterol/blood , Diabetes Mellitus, Type 2/metabolism , Diabetic Retinopathy/metabolism , Dyslipidemias/metabolism , Female , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged
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