MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells

Abstract Background Glioblastoma multiformae (GBM) is the most aggressive type of malignant brain tumor with complex molecular profile. Overexpression of Na+/H+ Exchanger isoform 9 (NHE9) promotes tumor progression and correlates positively with insensitivity to radiochemotherapy and poor prognosis. However, molecular mechanisms responsible for increase in NHE9 levels beyond a critical threshold have not been identified. Methods Bioinformatics analysis, luciferase reporter assays, real-time PCR and western blotting were conducted to examine the expression profiles and identify microRNAs (miRNA) that target NHE9. Cell proliferation and migration assays were conducted in U87 glioblastoma cells to determine the consequence of miRNA mediated targeting of NHE9. Endosomal pH measurements, immunofluorescence microscopy and surface biotinylation experiments were conducted to characterize the mechanistic basis of regulation. Results We show that microRNA 135a (miR-135a) targets NHE9 to downregulate its expression in U87 cells. MiR-135a levels are significantly lower in glioblastoma cells compared to normal brain tissue. Downregulation of NHE9 expression by miR-135a affects proliferative and migratory capacity of U87 cells. Selectively increasing NHE9 expression in these cells restored their ability to proliferate and migrate. We demonstrate that miR-135a takes a two-pronged approach affecting epidermal growth factor receptors (EGFRs) to suppress tumor cell growth and migration. EGFR activity is a potent stimulator of oncogenic signaling. While miR-135a targets EGFR transcripts to decrease the total number of receptors made, by targeting NHE9 it routes the few EGFRs made away from the plasma membrane to dampen oncogenic signaling. NHE9 is localized to sorting endosomes in glioblastoma cells where it alkalinizes the endosome lumen by leaking protons. Downregulation of NHE9 expression by miR-135a acidifies sorting endosomes limiting EGFR trafficking to the glioblastoma cell membrane. Conclusions We propose downregulation of miR-135a as a potential mechanism underlying the high NHE9 expression observed in subset of glioblastomas. Future studies should explore miR-135a as a potential therapeutic for glioblastomas with NHE9 overexpression.https://deepblue.lib.umich.edu/bitstream/2027.42/140393/1/12964_2017_Article_209.pd

Geochemical composition of dust from Qatar peninsula

Atmospheric dust samples have been collected from different areas in Qatar and analyzed for major and trace element composition. This region of the Arabian Gulf represents an area largely affected by dust from natural and anthropogenic sources. Twenty one samples were collected during 2014 and 2015 from Al-Khor, Katara, Sealine, Al-Waab, and Qatar University by passive and active sampling techniques. Some bulk samples were collected during the massive megastorm that occurred in April 2015. Back trajectories were determined for each sample set using the NOAA HYSPLIT model over a 50 hour time interval. Samples were equally divided between northerly (n=12; northern Saudi Arabia, Kuwait or Iraq) and southerly (n=8; SE Saudi Arabia, United Arab Emirates and Oman) sources. One sample is expected to originate from westward, in Saudi Arabia. There is more variability noticed in source locations throughout the winter months (October to March), with more of them coming from the south (9 times) compared to summer months (April to September) for twice only. Dust samples were microwave-assisted, total acid digested (HF+HCl+HNO3) and oxidized with H2O2 before analyses were conducted by ICP-OES. Only 12 out of 23 elements (Al, Ca, Fe, K, Mg, Na, Ag, As, Ba, Be, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Sr, V, Zn, P) of the Qatari dust samples were enriched relative to Upper Continental Crust (UCC). Calcium was especially enriched to a level of 400% relative to UCC. About 33% of the total sample mass was CaCO3, reflecting the composition of surface rocks in the source areas. Of the elements typically associated with anthropogenic activity, Ag, Ni, and Zn were the most enriched relative to UCC, with enrichment factors of 182%, 233%, and 209%, respectively. Other metals like Pb and V were not significantly enriched, with enrichment factors not exceeding 25% and 3%, respectively. Major elements (Al, Mn and Fe) were depleted relative to UCC due to the strong enrichment of CaCO3, with enrichment factors of -58%, -35% and -5%, respectively. Samples with northern and southern origins were separated to investigate if the elemental composition could be used to identify source/origin. Only three elements were observed to have a statistical difference. Pb and Na were higher in the samples collected from the south while Cr was higher in those from the north. This study aims to investigate present-day geochemistry of dust particles and its effect on the marine environment of the Arabian Gulf. The geochemical composition of dust is essential component for correcting lithogenic input to water column suspended matter samples.qscienc

Fig. 2. Observed HMBC correlations for 1–2 in Biofilm blocking sesquiterpenes from Teucrium polium

Fig. 2. Observed HMBC correlations for 1–2 as indicated by the arrows.Published as part of <i>Elmasri, Wael A., Hegazy, Mohamed-Elamir F., Aziz, Mina, Koksal, Ekrem, Amor, Wail, Mechref, Yehia, Hamood, Abdul N., Cordes, David B. & Paré, Paul W., 2014, Biofilm blocking sesquiterpenes from Teucrium polium, pp. 107-113 in Phytochemistry 103</i> on page 109, DOI: 10.1016/j.phytochem.2014.03.029, <a href="http://zenodo.org/record/10489548">http://zenodo.org/record/10489548</a&gt

Biofilm blocking sesquiterpenes from <em>Teucrium polium</em>

The chemical composition and antibacterial activity of Teucrium polium L. (Lamiaceae) were assessed; sixteen compounds were isolated from a CH2Cl2/MeOH extract of the aerial parts of the plant including four sesquiterpenes 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en-6 beta-ol-1-one, 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxy1,6 beta-ol, 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxy1,6 beta-ol and 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxyl,6 alpha-ol, together with seven known sesquiterpenes, one known iridoid glycoside, two known flavonoids, and one known phenylpropanoid glycoside. Structures were elucidated on the basis of spectroscopic (UV, H-1 and C-13 NMR) data, as well as two-dimensional NMR (H-1-H-1 COSY, HMQC, NOESY and HMBC), and ESI-MS analysis. The relative stereochemistiy of the ketone was established by X-ray crystallography, while its absolute configuration was attained by a modified Mosher's method. Antibacterial activity of the crude extract, as well as with four of the isolated metabolites, was observed with Staphylococcus aureus anti-biofilm activity in the low mu Mol range. Diverse sesquiterpene-skeleton structure and corresponding comprehensive enzyme capacity is discussed. </i

Biofilm blocking sesquiterpenes from <em>Teucrium polium</em>

The chemical composition and antibacterial activity of Teucrium polium L. (Lamiaceae) were assessed; sixteen compounds were isolated from a CH2Cl2/MeOH extract of the aerial parts of the plant including four sesquiterpenes 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en-6 beta-ol-1-one, 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxy1,6 beta-ol, 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxy1,6 beta-ol and 4 beta,5 alpha-epoxy-7 alpha H-germacr-10(14)-en,1 beta-hydroperoxyl,6 alpha-ol, together with seven known sesquiterpenes, one known iridoid glycoside, two known flavonoids, and one known phenylpropanoid glycoside. Structures were elucidated on the basis of spectroscopic (UV, H-1 and C-13 NMR) data, as well as two-dimensional NMR (H-1-H-1 COSY, HMQC, NOESY and HMBC), and ESI-MS analysis. The relative stereochemistiy of the ketone was established by X-ray crystallography, while its absolute configuration was attained by a modified Mosher's method. Antibacterial activity of the crude extract, as well as with four of the isolated metabolites, was observed with Staphylococcus aureus anti-biofilm activity in the low mu Mol range. Diverse sesquiterpene-skeleton structure and corresponding comprehensive enzyme capacity is discussed. </i

Prevalence of insomnia and relationship with depression, anxiety and stress among Jazan University students: A cross-sectional study

Insomnia, a common sleep disorder, is a public health concern, as it can lead to physical and mental exhaustion. The objective of this study was to determine the prevalence of insomnia and the common associated risk factors among students at Jazan University, in the Jazan region of southwestern Saudi Arabia. An observational cross-sectional study was conducted among a sample of 712 students. A pre-designed, structured questionnaire was used to collect the relevant information pertaining to the study variables. The overall prevalence of insomnia in the study was 19.3%. There was no significant difference in prevalence between males and females (p-value = 0.5). Participants from health colleges had greater prevalence of insomnia than those from art and Islamic colleges and science colleges (p-value = 0.03). Symptoms of depression, anxiety, and stress were significant risk factors for insomnia (p-value = 0.005, 0.000, 0.000, respectively). Insomnia is widely prevalent among Jazan University students. Symptoms of depression, anxiety, and stress, together with a noisy environment around the sleeping area, are important correlates. Screening for mental illnesses among university students is highly recommended

Multitargeted Flavonoid Inhibition of the Pathogenic Bacterium <i>Staphylococcus aureus</i>: A Proteomic Characterization

Growth inhibition of the pathogen Staphylococcus aureus with currently available antibiotics is problematic in part due to bacterial biofilm protection. Although recently characterized natural products, including 3′,4′,5-trihydroxy-6,7-dimethoxy-flavone [<b>1</b>], 3′,4′,5,6,7-pentahydroxy-flavone [<b>2</b>], and 5-hydroxy-4′,7-dimethoxy-flavone [<b>3</b>], exhibit both antibiotic and biofilm inhibitory activities, the mode of action of such hydroxylated flavonoids with respect to S. aureus inhibition is yet to be characterized. Enzymatic digestion and high-resolution MS analysis of differentially expressed proteins from S. aureus with and without exposure to antibiotic flavonoids (<b>1</b>–<b>3</b>) allowed for the characterization of global protein alterations induced by metabolite treatment. A total of 56, 92, and 110 proteins were differentially expressed with bacterial exposure to <b>1</b>, <b>2</b>, or <b>3</b>, respectively. The connectivity of the identified proteins was characterized using a search tool for the retrieval of interacting genes/proteins (STRING) with multitargeted S. aureus inhibition of energy metabolism and biosynthesis by the assayed flavonoids. Identifying the mode of action of natural products as antibacterial agents is expected to provide insight into the potential use of flavonoids alone or in combination with known therapeutic agents to effectively control S. aureus infection

The educational value of ward rounds as a learning and teaching opportunity for house officers, medical officers, and registrars in Sudanese hospitals: a multi-center cross-sectional study

Abstract Background Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors’ perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. Method A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors’ perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. Results A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. Conclusion Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice