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Background: Neck pain is the major cause of morbidity and absenteeism from university lessons among medical students worldwide. Medical students are more exposed and appear to have neck pain because of their length of study to achieve their professional goals. However, up to the knowledge of the researcher, there is a scarcity of literature conducted on prevalence and associated factors of neck pain among medical students in Ethiopia. Therefore, the aim of this study was to determine the prevalence and factors associated with neck pain among medical students at Mekelle University, College of Health Sciences, Tigray, Ethiopia., Method: Institutional based cross-sectional study was conducted from April 2018 to May 2018. A structured questionnaire adapted from the Nordic musculoskeletal questionnaire was distributed to 422 participants using a self-administered questionnaire in Mekelle University, College of Health Sciences Tigray, Ethiopia. Independent variables which had a significant association were identified using logistic regression models. Results were reported by using texts and frequency distribution tables., Result: A total of 422 participants involved in this study, with a 99.3% response rate. Previous 12 months self-reported prevalence of neck pain among medical students was found to be 49.2% with 95%CI (44.5-54%). Previous history of neck pain (AOR: 11.811, 95%CI: 5.460-25.549), physical exercise (AOR: 2.044, 95%CI: 1.233-3.387), duration of reading (AOR: 1.502, 95%CI: 0.236-2.780) and awkward posture (AOR: 3.87, 95%CI: 2.311-6.484) were factors significantly associated with neck pain., Conclusion and Recommendation: The current study showed that nearly half of the study participants self-reported to have suffered neck pain in the preceding 12 months. Past history of neck pain, physical exercise, duration of reading and awkward neck posture are likely to be significantly associated neck pain among medical students in Ethiopia. Engaging in consistent physical exercise has a protective effect against neck pain. Therefore, Medical students are recommended to carry out a regular physical exercise for a minimum of twenty to thirty minutes per day.

Scope: Hops contain the phytoestrogen, 8-prenylnaringenin, and the cytoprotective compound, xanthohumol (XH). XH induces the detoxification enzyme, NAD(P)H-quinone oxidoreductase (NQO1) in vitro; however, the tissue distribution of XH and 8-prenylnaringenin and their tissue-specific activity have not been analyzed., Methods and Results: An orally administered hop extract and subcutaneously injected XH were administered to Sprague-Dawley rats over 4 days. LC-MS-MS analysis of plasma, liver, and mammary gland revealed that XH accumulated in liver and mammary glands. Compared with the low level in the original extract, 8-prenylnaringenin was enriched in the tissues. Hops and XH-induced NQO1 in the liver, while only hops reduced NQO1 activity in the mammary gland. Mechanistic studies revealed that hops modulated NQO1 through three mechanisms. In liver cells, (i) XH modified Kelch-like ECH-associated protein leading to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation and antioxidant response element (ARE) activation; (ii) hop-mediated ARE induction was partially mediated through phosphorylation of Nrf2 by PKC; (iii) in breast cells, 8-prenylnaringenin reduced NQO1 likely through binding to estrogen receptorα, recruiting Nrf2, and downregulating ARE-regulated genes., Conclusion: XH and 8-prenylnaringenin in dietary hops are bioavailable to the target tissues. While hops and XH might be cytoprotective in the liver, 8-prenylnaringenin seems responsible for hop-mediated NQO1 reduction in the mammary gland., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

The roots of Angelica sinensis (Oliv.) Diels (Dang Gui; Apiaceae) have a long history in traditional Chinese medicine as a remedy for women's disorders and are often called "lady's ginseng". Currently, extracts of A. sinensis are commonly included in numerous dietary supplements used for women's health and as antiaging products. In the present study, we examined the potential chemopreventive activity of A. sinensis extracts by measuring the relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). The lipophilic partitions showed strong NQO1 induction with concentrations to double the enzyme activity (CD) of 5.5 +/- 0.7 (petroleum ether) and 3.9 +/- 0.5 microg/mL (chloroform). Fractionation led to the isolation of phenolic esters and alkylphthalides, especially Z-ligustilide, the main lipophilic compound, which showed strong NQO1 inducing properties (CD = 6.9 +/- 1.9 microM). Transcription of many detoxifying enzymes is regulated through the antioxidant response element (ARE) and its transcription factor Nrf2, which is repressed under basal conditions by Keap1. However, exposure to electrophilic inducers that alkylate Keap1 results in higher concentrations of free Nrf2 and ARE activation. The ARE reporter activity was therefore analyzed in HepG2-ARE-C8 cells after incubation with lipophilic extracts of A. sinensis or ligustilide for 24 h. Under these conditions, both the extract and the ligustilide increased ARE-luciferase reporter activity in a dose-dependent manner. Incubation of ligustilide with GSH and subsequent LC-MS-MS analysis revealed that ligustilide as well as oxidized ligustilide species covalently modified GSH. In addition, using MALDI-TOF mass spectrometry and LC-MS-MS, it was demonstrated that the lipophilic extracts, ligustilide, and monooxygenated ligustilide alkylated important cysteine residues in human Keap1 protein, thus activating Nrf2 and transcription of ARE regulated genes. These observations suggest that A. sinensis dietary supplements standardized to ligustilide have potential as chemopreventive agents through induction of detoxification enzymes.

Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural "linker" as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.

Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.