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      • Effects of Microgravity on Vestibular Development and Function in Rats: Genetics and Environment

        Ronca, April-E.,Fritzsch, Bernd,Alberts, Jeffrey-R.,Bruce, Laura-L. The Korean Society for Integrative Biology 2000 Korean journal of biological sciences Vol.4 No.3

        Our anatomical and behavioral studies of embryonic rats that developed in microgravity suggest that the vestibular sensory system, like the visual system, has genetically mediated precesses of development that establish crude connections between the periphery and the brain. Environmental stimuli also regulate connection formation including terminal branch formation and fine-tuning of synaptic contacts. Axons of vestibular sensory neurons from grabistatic as well as linear acceleration receptors reach their targets in both microgravity and norm81 gravity, suggesting that this is a genetically regulated component of development. However, microgravity exposure delays the development of terminal branches and synapses in gravistatic but not linear acceleration-sensitive neurons and also produces behavioral changes. These latter changes reflect environmentally controlled processes of development.

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        Efficacy of Nutraceutical Combination of Monacolin K, Berberine, and Silymarin on Lipid Profile and PCSK9 Plasma Level in a Cohort of Hypercholesterolemic Patients

        Elena Formisano,Andrea Pasta,Anna L. Cremonini,Elda Favari,Annalisa Ronca,Federico Carbone,Tommaso Semino,Francesco Di Pierro,Samir G. Sukkar,Livia Pisciotta 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.6

        The guidelines for the treatment of dyslipidemias include the use of nutraceuticals (NUTs) in association with lifestyle modifications to achieve therapeutic goals. In NUT pill, different substances may be associated; in this study we investigated a combined NUT containing monacolin K (MonK)+KA (1:1), berberine (BBR), and silymarin. The aim of the study was to evaluate low-density lipoprotein cholesterol (LDL-C) reduction in 53 patients suffering from polygenic hypercholesterolemia, characterized by a low/intermediate cardiovascular risk calculated with SCORE algorithm. The effects on lipid profile of 2-month treatment with NUT containing MonK+KA (1:1), BBR, and sylimarin, were compared with Atorvastatin (ATO) 10 mg administrated in a matched control group. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the cholesterol loading capacity (CLC) were determined at baseline and at the end of the study in NUT-treated group; variations were assessed. NUT was effective as lipid-lowering agent with a wide interindividual response variability (mean LDL-C from 170.8 ± 19.9 to 123.8 ± 20.0 with a change of −47.0 ± 21.5 mg/dL; P < .001) and the effect was similar to that induced by ATO. The use of NUT significantly modified PCSK9 levels (P < .01) and CLC (P < .001), ultimately suppressing the serum-mediated foam cell generation directly measured on human macrophages. NUT reduces LDL-C levels with an effect similar to what is induced by 10 mg of ATO and ex vivo improves the functional profile of lipoproteins with antiatherogenic action.

      • Telomere shortening and inactivation of cell cycle checkpoints characterize human hepatocarcinogenesis

        Plentz, Ruben Raphael,Park, Young Nyun,Lechel, André,Kim, Haeryoung,Nellessen, Friederike,Langkopf, Britta Heike Eva,Wilkens, Ludwig,Destro, Annarita,Fiamengo, Barbara,Manns, Michael Peter,Ronca Wiley Subscription Services, Inc., A Wiley Company 2007 Hepatology Vol.45 No.4

        <P>Telomere shortening and inactivation of cell cycle checkpoints characterize carcinogenesis. Whether these molecular features coincide at specific stages of human hepatocarcinogenesis is unknown. The preneoplasia–carcinoma sequence of human HCC is not well defined. Small cell changes (SCC) and large cell changes (LCC) are potential precursor lesions. We analyzed hepatocellular telomere length, the prevalence of DNA damage, and the expression of p21 and p16 in biopsy specimens of patients with chronic liver disease (n = 27) that showed different precursor lesions and/or HCC: liver cirrhosis (n = 25), LCC (n = 26), SCC (n = 13), and HCC (n = 13). The study shows a decrease in telomere length in nondysplastic cirrhotic liver compared with normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres, followed by SCC and LCC. Hepatocytes showed an increased p21 labeling index (p21-LI) at the cirrhosis stage, which remained elevated in most LCC. In contrast, most SCC and HCC showed a strongly reduced p21-LI. Similarly, p16 was strongly expressed in LCC but reduced in SCC and not detectable in HCC. γH2AX-DNA-damage-foci were not detected in LCC but were present in SCC and more frequently in HCC. These data indicate that LCC and SCC represent clonal expansions of hepatocytes with shortened telomeres. Conclusion: The inactivation of cell cycle checkpoints coincides with further telomere shortening and an accumulation of DNA damage in SCC and HCC, suggesting that SCC represent more advanced precursor lesions compared with LCC. (HEPATOLOGY 2007;45:968–976.)</P>

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