Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

<p>Abstract</p> <p>Background</p> <p>High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin.</p> <p>Methods</p> <p>Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in male <it>Wistar </it>rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days.</p> <p>Results</p> <p>Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration.</p> <p>Conclusion</p> <p>Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic abnormalities induced by this diet model except for HHcy.</p

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations

Internet-based search of randomised trials relevant to mental health originating in the Arab world

BACKGROUND: The internet is becoming a widely used source of accessing medical research through various on-line databases. This instant access to information is of benefit to busy clinicians and service users around the world. The population of the Arab World is comparable to that of the United States, yet it is widely believed to have a greatly contrasting output of randomised controlled trials related to mental health. This study was designed to investigate the existence of such research in the Arab World and also to investigate the availability of this research on-line. METHODS: Survey of findings from three internet-based potential sources of randomised trials originating from the Arab world and relevant to mental health care. RESULTS: A manual search of an Arabic online current contents service identified 3 studies, MEDLINE, EMBASE, and PsycINFO searches identified only 1 study, and a manual search of a specifically indexed, study-based mental health database, PsiTri, revealed 27 trials. CONCLUSION: There genuinely seem to be few trials from the Arab world and accessing these on-line was problematic. Replication of some studies that guide psychiatric/psychological practice in the Arab world would seem prudent

Miswired Enhancer Logic Drives a Cancer of the Muscle Lineage

Core regulatory transcription factors (CR TFs) establish enhancers with logical ordering during embryogenesis and development. Here we report that in fusion-positive rhabdomyosarcoma, a cancer of the muscle lineage, the chief oncogene PAX3-FOXO1 is driven by a translocated FOXO1 super enhancer (SE) restricted to a late stage of myogenesis. Using chromatin conformation capture techniques, we demonstrate that the extensive FOXO1 cis-regulatory domain interacts with PAX3. Furthermore, RNA sequencing and chromatin immunoprecipitation sequencing data in tumors bearing rare PAX translocations implicate enhancer miswiring across all fusion-positive tumors. HiChIP of H3K27ac showed connectivity between the FOXO1 SE, additional intra-domain enhancers, and the PAX3 promoter. We show that PAX3-FOXO1 transcription is diminished when this network of enhancers is ablated by CRISPR. Our data reveal a hijacked enhancer network that disrupts the stepwise CR TF logic of normal skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an "infinite loop" enhancer logic that locks rhabdomyosarcoma in an undifferentiated stage

The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure

The Origin Recognition Complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre- RC complexes at origins of DNA replication. Here we report tiling-sgRNA CRISPR screens that show that each subunit of ORC and CDC6 are essential in human cells. Using an auxin-inducible degradation system, stable cell lines were created that ablate ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defect in the absence of ORC2 was cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2 deficient cells were also large, with decompacted heterochromatin. Some ORC2 deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization

Apple polyphenols in human and animal health*

Apples contain substantial amounts of polyphenols, and diverse phenolics mainly flavonoids and phenolic acids, have been identified in their flesh and skins. This work aimed to analyze the overall landscape of the research literature published to date on apple phenolic compounds in the context of human and animal health. The Web of Science Core Collection electronic database was queried with (apple* polyphenol*) AND (health* OR illness* OR disease* OR medic* OR pharma*) to identify relevant papers covering these words and their derivatives in the titles, abstracts, and keywords. The resulted 890 papers were bibliometrically analyzed. The VOSviewer software was utilized to produce term maps that illustrate how the frequent phrases fared in terms of publication and citation data. The apple polyphenol papers received global contributions, particularly from China, Italy, the United States, Spain, and Germany. Examples of frequently mentioned chemicals/chemical classes are quercetin, anthocyanin, catechin, epicatechin, and flavonol, while examples of frequently mentioned medical conditions are cardiovascular disease, atherosclerosis, diabetes, Alzheimers disease, and obesity. The potential health benefits of apple polyphenols on humans and animals are diverse and warrant further study.Authors acknowledge the support from The National Centre for Research and Development (NCBR) of Poland (project number POIR.01.01.01-00-0593/18).info:eu-repo/semantics/publishedVersio

Miswired Enhancer Logic Drives a Cancer of the Muscle Lineage.

Core regulatory transcription factors (CR TFs) establish enhancers with logical ordering during embryogenesis and development. Here we report that in fusion-positive rhabdomyosarcoma, a cancer of the muscle lineage, the chief oncogene PAX3-FOXO1 is driven by a translocated FOXO1 super enhancer (SE) restricted to a late stage of myogenesis. Using chromatin conformation capture techniques, we demonstrate that the extensive FOXO1 cis-regulatory domain interacts with PAX3. Furthermore, RNA sequencing and chromatin immunoprecipitation sequencing data in tumors bearing rare PAX translocations implicate enhancer miswiring across all fusion-positive tumors. HiChIP of H3K27ac showed connectivity between the FOXO1 SE, additional intra-domain enhancers, and the PAX3 promoter. We show that PAX3-FOXO1 transcription is diminished when this network of enhancers is ablated by CRISPR. Our data reveal a hijacked enhancer network that disrupts the stepwise CR TF logic of normal skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an "infinite loop" enhancer logic that locks rhabdomyosarcoma in an undifferentiated stage

The effect of an extract from Ganoderma lucidum (reishi) on the labeling of blood constituents with technetium-99m and on the survival of Escherichia coli

This study evaluated effects of an aqueous extract of Ganoderma lucidum (reishi) on the labeling of blood constituents with technetium-99m (99mTc) and on the survival of cultures of Escherichia coli treated with stannous chloride. Blood samples from Wistar rats were treated with reishi extract, radiolabeling procedure was performed, plasma (P), blood cells (BC) and insoluble (IF) and soluble (SF) fractions of P and BC were separated. The radioactivity was counted for the determination of the percentages of radioactivity (%ATI). Cultures of Escherichia coli AB1157 were treated with stannous chloride in the presence and absence of reishi extract. Blood samples and bacterial cultures treated with NaCl 0.9% were used as controls. Data indicated that reishi extract altered significantly (p99mTc and protecting bacterial cultures against oxidative damage induced by stannous chloride

The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells

Reactivation of fetal hemoglobin (HbF) production benefits patients with sickle cell disease and beta-thalassemia. To identify new HbF regulators that might be amenable to pharmacologic control, we screened a protein domain-focused CRISPR-Cas9 library targeting chromatin regulators, including BTB domain-containing proteins. Speckle-type POZ protein (SPOP), a substrate adaptor of the CUL3 ubiquitin ligase complex, emerged as a novel HbF repressor. Depletion of SPOP or overexpression of a dominant negative version significantly raised fetal globin messenger RNA and protein levels with minimal detrimental effects on normal erythroid maturation, as determined by transcriptome and proteome analyses. SPOP controls HbF expression independently of the major transcriptional HbF repressors BCL11A and LRF. Finally, pharmacologic HbF inducers cooperate with SPOP depletion during HbF upregulation. Our study implicates SPOP and the CUL3 ubiquitin ligase system in controlling HbF production in human erythroid cells and may offer new therapeutic strategies for the treatment of beta-hemoglobinopathies

Antioksidativni učinci N-acetilcisteina, lipoične kiseline, taurina i kurkumina u mišićnom tkivu šarana (Cyprinus carpio L.) tretiranih kadmijem

We investigated the muscle tissue of a teleost Cyprinus carpio L. to find out whether N-acetylcysteine (NAC), alpha-lipoic acid (LA), taurine (TAU), and curcumin (CUR) were able to counteract oxidative stress induced by acute exposure to cadmium (Cd). The muscle tissue was dissected 96 h after a single intraperitoneal injection of Cd (5 mg kg-1) and of antioxidant substances (50 mg kg-1). Using spectrophotometry, we determined the glutathione redox status, lipid peroxidation levels and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione disulphide reductase (GR). Accumulation of Cd in the muscle was analysed using inductively coupled plasma - optical emission spectrometry (ICP-OES). All substances lowered Cd levels in the following order of effi ciency; LA=NAC>TAU=CUR. Cadmium increased SOD activity, but CAT activity declined, regardless of antioxidant treatment. Treatment with CUR induced GPx activity. Treatment with TAU lowered Cd due to higher total glutathione (tGSH). The most effective substances on lipid peroxidation were LA and NAC due to a greater Cd-lowering potential. It seems that the protective role of TAU, LA, and NAC is not necessarily associated with antioxidant enzymes, but rather with their own activity.Cilj istraživanja bio je utvrditi mogu li N-acetilcistein (NAC), α-lipoična kiselina (LA), taurin (TAU) i kurkumin (CUR) svojim antioksidativnim djelovanjem smanjiti razinu oksidativnog stresa u mišićnom tkivu šarana (Cyprinus carpio L.) akutno otrovanih kadmijem. Uzorci mišićnog tkiva skupljeni su 96 h nakon što su ribama intraperitonealno injicirani kadmij (5 mg kg-1) i ispitivani antioksidansi (50 mg kg-1). Primjenom spektrofotometrijskih metoda izmjereni su redoks status glutationa, razine lipidne peroksidacije te aktivnosti enzima superoksid dismutaze (SOD), katalaze (CAT), glutation peroksidaze (GPx) i glutation disulfi d reduktaze (GR). Maseni udio kadmija u mišićnom tkivu izmjeren je s pomoću metode induktivno spregnute plazme – optičke emisijske spektrometrije (ICP-OES). Ispitivani spojevi smanjili su nakupljanje kadmija u tkivu šarana sljedećim redoslijedom: LA=NAC>TAU=CUR. Tretman šarana kadmijem izazvao je porast aktivnosti SOD, ali se aktivnost CAT smanjila bez obzira na primjenu antioksidativnih spojeva. Dodatak CUR pojačao je aktivnost GPx. Dodatak TAU povećao je razinu ukupnoga glutationa te smanjio nakupljanje kadmija. Svi spojevi osim CUR smanjili su razinu lipidne peroksidacije te pretpostavljamo da su LA i NAC pridonijeli detoksifi kaciji kadmija. Rezultati istraživanja upućuju na to da testirani spojevi, osim CUR, imaju antioksidativni učina