Effects of free and nanoparticulate curcumin on chemically induced liver carcinoma in an animal model

IntroductionCurcumin therapeutic applications are constrained by its prominent metabolic instability as well as inadequate absorption and bioavailability. The current study was designed to enhance the curcumin bioavailability by exploiting nanoparticles.Material and methodsEleven groups of mice were divided into: normal and nanoparticle control groups, a hepatocellular carcinoma (HCC) group induced by diethylnitrosamine (DEN), 2 groups treated with DEN plus a high dose/low dose of free curcumin, 2 groups treated with a high dose/low dose of free curcumin, 2 groups treated with DEN plus a high dose/low dose of nanoparticulate curcumin, and 2 groups treated with a high dose/low dose of nanoparticulate curcumin.ResultsDEN administration significantly increased liver enzymes, vascular endothelial growth factor, tumor necrosis factor-α, α-fetoprotein, malondialdehyde, and nucelar factor-κB. Also, it decreased serum albumin and tissue antioxidant activities and caused severe histological changes in hepatic tissue. Oral treatment of DEN-injected mice with either a high dose of free curcumin or the tested doses of nanoparticulate curcumin resulted in a significant improvement of all the tested parameters.ConclusionsAlthough the two tested doses of nanoparticulate curcumin were much lower than free curcumin, both doses were effective in preventing HCC development while the low dose of free curcumin was hardly effective. Hence, we conclude that nanoparticles enhance the bioavailability of curcumin.     

Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.

Aging is an unavoidable fate that afflicts all life, during this process in mammals, reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging.     

Expression of Leptin and Visfatin in Gingival Tissues of Chronic Periodontitis With and Without Type 2 Diabetes Mellitus: A Study Using Enzyme‐Linked Immunosorbent Assay and Real‐Time Polymerase Chain Reaction

Background: The aim of this study is to investigate the protein and gene expression of leptin and visfatin in gingival tissue from patients with chronic periodontitis (CP), patients with CP and type 2 diabetes mellitus (T2DM), and healthy individuals. Methods: The study includes 50 individuals: 10 healthy individuals, 20 patients with CP, and 20 patients with CP and T2DM. Plaque index, gingival index, probing depth, and clinical attachment loss were measured, and gingival biopsies were obtained. Leptin and visfatin protein expression in gingival tissues was determined using enzyme‐linked immunosorbent assay, and messenger RNA (mRNA) expression was measured via real‐time polymerase chain reaction. Results: The highest leptin mRNA and protein expression was observed in the control group and was significantly (P ≤0.05) different from the CP and CP+T2DM groups. Gingival tissues from patients with CP and T2DM had a significant increase in visfatin and a decrease in leptin gene and protein expression (P <0.05) compared with both controls and patients with CP. Conclusion: Expression of leptin and visfatin in the gingival tissues suggests a possible role for these adipokines in the pathogenesis of CP and T2DM.     

Identification of Candidate Long Noncoding RNAs Associated with Left Ventricular Hypertrophy

Purpose

Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.

Methods

Wild‐type and adenosine A2A receptor overexpressing mice (A2A‐Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome‐wide microarrays and an analytical pipeline specifically developed for lncRNAs.

Results

Microarray analysis identified two lncRNAs up‐regulated and three down‐regulated in the hearts of A2A‐Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A‐Tg mice (3.5‐ and 1.8‐fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham‐operated animals (1.8‐ and 1.4‐fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2‐ and 1.6‐fold (p < 0.01).

Conclusions

First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart.     

Radiographic assessment of impacted teeth and associated pathosis prevalence: Pattern of occurrence at different ages in Saudi male in Western Saudi Arabia

Objectives:

To assess the prevalence of both impaction and associated pathosis in a Saudi population in Al-Madinah, Saudi Arabia based on digital panoramic radiographs.

Methods:

This study was carried out from December 2013 to February 2015. Panoramic radiographs of 359 male patients attending the Oral Diagnosis Clinics, Faculty of Dentistry, Taibah University, Al-Madinah, Saudi Arabia were reviewed. All images were evaluated to determine the prevalence and pattern of impacted third molars and canines, and associated pathosis.

Results:

Among 359 panoramic radiographs examined, 124 patients had impacted teeth. The impacted mandibular third molars were the most prevalent impacted teeth, 77.6% had class II pattern of impaction. Among the impacted maxillary canines, 75% were mesioangular and among 66 impacted maxillary third molars, 63.6% had class C. Our study showed that 5.8% of Saudi patients had 3 or more impacted teeth, 13.1% had 2 impacted teeth, and 15.6% had one impacted tooth. Associated pathosis was found in 18.2% among impacted maxillary third molars, and 31.5% among impacted mandibular third molars. The incidence of impaction decreases with age.

Conclusion:

The prevalence and pattern of impacted third molars among Saudis are almost similar to other racial populations. The number of missing wisdom increases with age. Although the percentage of pathosis associated with impaction was considerably low, it is essential to carry you regular oral examinations to preserve asymptomatic impacted teeth in good health.As eruption is a complex process, therefore tooth retardation or failure of eruption may arise, so failure of permanent teeth eruption and subsequent impaction is a common dental anomaly.1 Previous literature reported that teeth impaction is a usual incident and many factors affect its prevalence including aging and eruption time.2 Genetic and environmental factors play a role in developmental disturbances. The incidence of impacted teeth is contradictory in different populations and ethnic groups.3 Complications associated with impaction may range from simple problems to serious life threatening problems. Hyperplastic follicular space, subsequent dentigerous cyst or odontogenic keratocyst are the most common simple problems with impaction.4,5 Serious complications involve malignant transformation of cystic wall into squamous cell carcinoma or mucoepidermoid carcinoma. Consequently, life threatening conditions maybe a chain of simple problem such as impaction, which if solved from the beginning would cost less, and would be simple to solve.6 Panoramic radiography is a simple tomographic technique that introduces the panoramic view of the maxillofacial region.7 Radiographic examinations are either digital imaging or conventional. Digital imaging has many advantages versus conventional, such as reduction of radiation exposure, feasibility of image manipulation and analysis, which improves sensitivity and diminishes errors.8 The United States guidelines state that the panoramic radiograph is one of the screening images for Adolescent with Permanent Dentition and Adult, Dentate or Partially Edentulous.9 During our daily oral examinations, we notice poor patient awareness of oral health and its implications in Saudi Arabia. Additionally, there is no present data on the prevalence of impacted teeth, and associated pathologies in the Saudi population in Al-Madinah, Saudi Arabia. The aim of the present study was to determine the prevalence and pattern of occurrence of impacted teeth at different ages based on digital panoramic radiograph. In addition, to report the radiographic features of associated pathologies in a Saudi male population, in order to correlate between impaction and associated pathosis     

Exploring end of life priorities in Saudi males: usefulness of Q-methodology

Background

Quality end-of-life care depends on understanding patients’ end-of-life choices. Individuals and cultures may hold end-of-life priorities at different hierarchy. Forced ranking rather than independent rating, and by-person factor analysis rather than averaging may reveal otherwise masked typologies.

Methods

We explored Saudi males’ forced-ranked, end-of-life priorities and dis-priorities. Respondents (n?=?120) rank-ordered 47 opinion statements on end-of-life care following a 9-category symmetrical distribution. Statements’ scores were analyzed by averaging analysis and factor analysis (Q-methodology).

Results

Respondents’ mean age was 32.1 years (range, 18–65); 52 % reported average religiosity, 88 and 83 %?≥?very good health and life-quality, respectively, and 100 %?≥?high school education. Averaging analysis revealed that the extreme five end-of-life priorities were to, be at peace with God, be able to say the statement of faith, maintain dignity, resolve conflicts, and have religious death rituals respected, respectively. The extreme five dis-priorities were to, die in the hospital, not receive intensive care if in coma, die at peak of life, be informed about impending death by family/friends rather than doctor, and keep medical status confidential from family/friends, respectively. Q-methodology classified 67 % of respondents into five highly transcendent opinion types. Type-I (rituals-averse, family-caring, monitoring-coping, life-quality-concerned) and Type-V (rituals-apt, family-centered, neutral-coping, life-quantity-concerned) reported the lowest and highest religiosity, respectively. Type-II (rituals-apt, family-dependent, monitoring-coping, life-quantity-concerned) and Type-III (rituals-silent, self/family-neutral, avoidance-coping, life-quality & quantity-concerned) reported the best and worst life-quality, respectively. Type-I respondents were the oldest with the lowest general health, in contrast to Type-IV (rituals-apt, self-centered, monitoring-coping, life-quality/quantity-neutral). Of the extreme 14 priorities/dis-priorities for the five types, 29, 14, 14, 50, and 36 %, respectively, were not among the extreme 20 priorities/dis-priorities identified by averaging analysis for the entire cohort.

Conclusions

1) Transcendence was the extreme end-of-life priority, and dying in the hospital was the extreme dis-priority. 2) Quality of life was conceptualized differently with less emphasize on its physiological aspects. 3) Disclosure of terminal illness to family/close friends was preferred as long it is through the patient. 4) Q-methodology identified five types of constellations of end-of-life priorities and dis-priorities that may be related to respondents’ demographics and are partially masked by averaging analysis.

     

The effect of cannabis on oxidative stress and neurodegeneration induced by intrastriatal rotenone injection in rats

We investigated the effect of cannabis treatment on the development of oxidative stress and nigrostriatal cell injury induced by intrastriatal rotenone injection in rats. Rotenone was injected into the right striatum at a concentration of 5 mM (3 μl/rat). The control rats received the vehicle (DMSO). Subsequently, the effect of Cannabis sativa extract treatment on rotenone toxicity was evaluated. Starting on the second day of rotenone injection, rats were treated with C. sativa extract (5, 10, or 15 mg/kg) (expressed as Δ⁹-tetrahydrocannabinol) subcutaneously (s.c.) once daily for 30 days. Biochemical markers of oxidative stress, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase 1 (PON1) activity, catalase activity, as well as tumor necrosis factor alpha (TNF-α), were determined in different brain areas after 30 days of rotenone treatment. Histopathology and immunohistochemical expression of tyrosine hydroxylase (TH), capase 3, and inducible nitric oxide synthase (iNOS) were also performed. Results showed that intrastriatal injection of rotenone resulted in increased brain oxidative stress in the cerebral cortex, striatum, hippocampus, midbrain, and cerebellum. MDA increased by 41.4–70 %, nitric oxide increased by 48.3–77.5 %, while GSH decreased by 25.0–34.2 %. PON1 and catalase activities decreased by 43.0–60.8 % and by 14.2–36 %, respectively, in these areas. Striatal TNF-α increased by 638.9 % of control value after rotenone injection. Rotenone induced motor deficits (decreased rearing activity). Rotenone caused marked nigrostriatal neurodegeneration, decreased TH immunoreactivity, and increased both iNOS and caspase 3 immunoreactivities in the striatum. Cannabis decreased brain oxidative stress and nitric oxide release induced by intrastriatal rotenone in several brain areas. Cannabis also decreased the elevated TNF-α in the striatum. Cannabis did not protect against the immunohistochemical changes in the striatum and substantia nigra or against neuronal degeneration induced by rotenone treatment. Collectively, these results indicated that the administration of cannabis did not protect against nigrostriatal damage caused by intrastriatal rotenone.     

Platelet-albumin-bilirubin score-a predictor of outcome of acute variceal bleeding in patients with cirrhosis

BACKGROUND The albumin-bilirubin(ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin(PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation.AIM To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.METHODS The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh(CTP) class, Model of End-stage Liver Disease(MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receivingoperator characteristic curve(AUROC) were calculated for survival and rebleeding.RESULTS Mean age was 52.6 years; 1176 were male(77.5%), 69 CTP-A(4.5%), 434 CTP-B(29.2%), 1014 CTP-C(66.8%); 306 PALBI-1(20.2%), 285 PALBI-2(18.8%), and 926 PALBI-3(61.1%). Three hundred and thirty-two patients died during hospitalization(21.9%). Bleeding-related mortality occurred in 11% of CTP-B,28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively.CONCLUSION PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.     

Corneal elevation indices and pachymetry values of Saudi myopes using scheimpflug imaging

Objectives:To report the corneal elevation and thickness values for Saudi myopes and to evaluate the differences between these parameters in subgroups of this target population.Methods:Pentacam corneal topographic maps of the right eyes of patients visiting Al-Hokama Eye Clinic, Riyadh, Saudi Arabia, a tertiary eye center between January 2009 and December 2015 were retrospectively analyzed in this cross-sectional study. The patients were grouped into 3 categories based on their spherical readings: mild (-0.25 to -2.75D), moderate (-3.00 to -5.75D), and severe (≥-6.00D). Furthermore, patients with cylindrical readings of ≥-1.00 diopter were categorized as having myopic astigmatism, whereas those with less than -1.00 cylindrical diopter were categorized as having simple myopia.Results:Our sample was comprised of 1,276 patients; 838 (65.7%) had simple myopia and 438 (34.3%) had myopic astigmatism. The values for the whole myopic group were as follows: anterior corneal elevation (AE) at the apex= 2.60±1.48 (standard deviation), thinnest AE= 2.56±1.68, posterior elevation (PE) at the apex= 3.67±3.58, thinnest PE= 4.92±3.81, central pachymetry= 550.09±34.29, apical pachymetry=550.73±34.64, and thinnest pachymetry= 546.30±34.61. All of the measurements, except the apical PE and thinnest PE, were statistically significant across the simple and myopic astigmatism groups (p<0.05). Comparing the mild to moderate myopia groups revealed a significant difference in the apical AE (p=0.037). Moreover, the comparison between the mild and severe myopia groups revealed that the apical PE and the thinnest PE, as well as the central, apical, and thinnest pachymetry values were statistically significantly different (p<0.05).Conclusion:The corneal elevation indices and thicknesses specific to the Saudi myopes were found to be comparable to the international databases in terms of the elevation and thickness in some of the parameters.