Search results for: hepatic metabolism

Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Rattanathip Rattanachai, Piyachai Petchyen, Kunyanuth Kularbphettong

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This paper describes the development of a Weight- Balancing Control System based on the Android Operating System and it provides recommendations on ways of balancing of user’s weight based on daily metabolism process and need so that user can make informed decisions on his or her weight controls. The system also depicts more information on nutrition details. Furthermore, it was designed to suggest to users what kinds of foods they should eat and how to exercise in the right ways. We describe the design methods and functional components of this prototype. To evaluate the system performance, questionnaires for system usability and Black Box Testing were used to measure expert and user satisfaction. The results were satisfactory as followed: Means for experts and users were 3.94 and 4.07 respectively.

Keywords: weight-balancing control, Android operating system, daily metabolism, black box testing

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Authors: Magdalena Smoktunowicz, Renata Wawrzyniak, Malgorzata Waleron, Krzysztof Waleron

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Pectobacterium spp. were previously classified into the Erwinia genus founded in 1917 to unite at that time all Gram-negative, fermentative, nonsporulating and peritrichous flagellated plant pathogenic bacteria. After work of Waldee (1945), on Approved Lists of Bacterial Names and bacteriology manuals in 1980, they were described either under the species named Erwinia or Pectobacterium. The Pectobacterium genus was formally described in 1998 of 265 Pectobacterium strains. Currently, there are 21 species of Pectobacterium bacteria, including Pectobacterium betavasculorum since 2003, which caused soft rot on sugar beet tubers. Based on the biochemical experiments carried out for this, it is known that these bacteria are gram-negative, catalase-positive, oxidase-negative, facultatively anaerobic, using gelatin and causing symptoms of soft rot on potato and sugar beet tubers. The mere fact of growing on sugar beet may indicate a metabolism characteristic only for this species. Metabolomics, broadly defined as the biology of the metabolic systems, which allows to make comprehensive measurements of metabolites. Metabolomics, in combination with genomics, are complementary tools for the identification of metabolites and their reactions, and thus for the reconstruction of metabolic networks. The aim of this study was to apply the GC-MS-based untargeted metabolomics to study the metabolism of P. betavasculorum in different growing conditions. The metabolomic profiles of biomass and biomass media were determined. For sample preparation the following protocol was used: extraction with 900 µl of methanol: chloroform: water mixture (10: 3: 1, v: v) were added to 900 µl of biomass from the bottom of the tube and up to 900 µl of nutrient medium from the bacterial biomass. After centrifugation (13,000 x g, 15 min, 4oC), 300µL of the obtained supernatants were concentrated by rotary vacuum and evaporated to dryness. Afterwards, two-step derivatization procedure was performed before GC-MS analyses. The obtained results were subjected to statistical calculations with the use of both uni- and multivariate tests. The obtained results were evaluated using KEGG database, to asses which metabolic pathways are activated and which genes are responsible for it, during the metabolism of given substrates contained in the growing environment. The observed metabolic changes, combined with biochemical and physiological tests, may enable pathway discovery, regulatory inference and understanding of the homeostatic abilities of P. betavasculorum.

Keywords: GC-MS chromatograpfy, metabolomics, metabolism, pectobacterium strains, pectobacterium betavasculorum

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Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

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Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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Authors: Leelavinothan Pari , Ayyasamy Rathinam

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Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

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Authors: Girgis Younan, Ikram Eltayeb

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Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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Authors: Jiang Xu, Daoping Wang, Qun Li, Yinghong Pan

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2,4-Epibrassinolide (EBR), which is a kind of plant hormone Brassinosteroids (BRs), is widely studied and applied in the global scale but the proteomic characteristics of EBR alleviating low temperature stress in rice seedling leaves are still not clear. In this study, seeding rice of Nipponbare were treated with EBR and distilled water, then stressed at 4℃ or 26 ℃, and analyzed by mass spectrometry analysis, verified by parallel reaction monitoring technique (PRM). The results showed that 5778 proteins were identified in total and 4834 proteins were identified with quantitative information. Among them, 401 up-regulated and 220 down-regulated proteins may be related to EBR alleviating low temperature stress in rice seedling leaves. The molecular functions of most of up-regulated proteins are RNA binding and hydrolase activity and are mainly enriched in the pathways of carbon metabolism, folic acid synthesis, and amino acid biosynthesis. The down-regulated proteins are mainly related to catalytic activity and oxidoreductase activity and are mainly enriched in the pathways of limonene and pinene degradation, riboflavin metabolism, porphyrin and chlorophyll metabolism, and other metabolic pathways. PRM validation and literature analysis showed that NADP-malic acidase, peroxidase, 3-phosphoglycerate dehydrogenase, enolase, glyceraldehyde-3- phosphate dehydrogenase and pyruvate kinase are closely related to the effect of EBR on low temperature stress. These results also suggested that BRs could relieve the effect of low temperature stress on rice seed germination in many ways.

Keywords: 2, 4-Epibrassinolid, low temperature stress, proteomic analysis, rice

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Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Sara Arafeh, Kovriguine Evguine

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Cytochromes P450 are enzymes that require a supply of electrons to catalyze the synthesis of steroid hormones, fatty acids, and prostaglandin hormone. Cytochrome P450 Oxidoreductase (CYPOR), a membrane bound enzyme, provides these electrons in its open conformation. CYPOR has two cytosolic domains (FAD domain and FMN domain) and an N-terminal in the membrane. In its open conformation, electrons flow from NADPH, FAD, and finally to FMN where cytochrome P450 picks up these electrons. In the closed conformation, cytochrome P450 does not bind to the FMN domain to take the electrons. It was found that when the cytosolic domains are isolated, CYPOR could not bind to cytochrome P450. This suggested that the membrane environment is important for CYPOR function. This project takes the initiative to better understand the dynamics of CYPOR in its full length. Here, we determine the distance between specific sites in the FAD and FMN binding domains in CYPOR by Forster Resonance Energy Transfer (FRET) and Ultrafast TA spectroscopy with and without NADPH. The approach to determine these distances will rely on labeling these sites with red and infrared fluorophores. Mimic membrane attachment is done by inserting CYPOR in lipid nanodiscs. By determining the distances between the donor-acceptor sites in these domains, we can observe the open/closed conformations upon reducing CYPOR in the presence and absence of cytochrome P450. Such study is important to better understand CYPOR mechanism of action in various endosomal membranes including hepatic CYPOR which is vital in plasma cholesterol homeostasis. By investigating the conformational cycles of CYPOR, we can synthesize drugs that would be more efficient in affecting the steroid hormonal levels and metabolism of toxins catalyzed by Cytochrome P450.

Keywords: conformational cycle of CYPOR, cytochrome P450, cytochrome P450 oxidoreductase, FAD domain, FMN domain, FRET, Ultrafast TA Spectroscopy

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Authors: Nicole Pearcy, Jonathan J. Crofts, Nadia Chuzhanova

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In this paper, we employ a directed hypergraph model to investigate the extent to which environmental variability influences the set of available biochemical reactions within a living cell. Such an approach avoids the limitations of the usual complex network formalism by allowing for the multilateral relationships (i.e. connections involving more than two nodes) that naturally occur within many biological processes. More specifically, we extend the concept of network reciprocity to complex hyper-networks, thus enabling us to characterize a network in terms of the existence of mutual hyper-connections, which may be considered a proxy for metabolic network complexity. To demonstrate these ideas, we study 115 metabolic hyper-networks of bacteria, each of which can be classified into one of 6 increasingly varied habitats. In particular, we found that reciprocity increases significantly with increased environmental variability, supporting the view that organism adaptability leads to increased complexities in the resultant biochemical networks.

Keywords: complexity, hypergraphs, reciprocity, metabolism

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Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

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Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Chiagoziem A. Otuechere, Ebenezer O. Farombi

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The protective effect of dichloromethane: methanol extract of Pterocarpus mildbraedii (PME), a widely consumed Nigerian leafy vegetable, on the toxicity of propanil was investigated in male rats. Animals were distributed into eight groups of five each. Group 1 served as control and received normal saline while rats in groups 2, 3, and 4 received 100 mg/kg, 200 mg/kg, and 400 mg/kg extract doses respectively. Group 5 rats were orally administered 200 mg/kg propanil while groups 6, 7, and 8 rats were given propanil plus extract. Oral administration of propanil elicited a 14.8%, 5%, 122%, and 78% increase in the activity of serum enzymes; alanine aminotransferase (AST), alanine aminotransferase(ALT), Alkaline phoshatase (ALP) and Gamma glutamyl transferase (ﻻGT). There were also increase in Lactate dehydrogenase (LDH) activity, direct bilirubin and lipid peroxidation levels. Furthermore, PME significantly attenuated the marked hepatic oxidative damage that accompanied propanil treatment. The extract significantly decreased LDH activity and bilirubin levels following propanil treatment. Furthermore, propanil-induced alterations in the activities of antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT) and glutathione s-transferase (GST) in these rats were modulated by the extract. The percentage DPPH Radical Scavenging Activity of the extract was determined as 55% and compared to those of Gallic acid (49%). Hepatic histology examination further confirmed the damage to the liver as it revealed severe periportal cellular infiltration of the hepatocytes. These biochemical and morphological alterations were attenuated in rats pre-treated with 100 mg/kg and 200 mg/kg doses of the extract. These results suggest that PME possesses protective effect against propanil-induced hepatotoxicity.

Keywords: antioxidant, hepatoprotection, Pterocarpus mildbraedii, propanil

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Authors: Walaa Mohammed Saeed

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Studies suggest a crosstalk between bone and metabolism through Osteocalcin (OC), a bone-derived protein that plays an important role in regulating glucose and fat metabolism. Studies relate type II Diabetes Mellitus (DMII) with Homocysteine (Hcy) and cardiovascular diseases (CVD). This study investigates the relationship between levels of OC, Hcy, and DMII in 85 subjects of which 50 were diabetic female patients (29–65 years) and 35 healthy controls. OC and Hcy levels were measured in fasting blood samples using immunoassay analyzer. Fasting serum glucose, glycated hemoglobin, lipid profile, were estimated by automated Siemens Dimension XP auto-analyzer. A significant increase in the frequency of low OC levels (p < 0.001) and high Hcy levels (p < 0.001) was detected in diabetic patients compared to controls (chi-squared test). Using ANOVA test, patients were divided into tertiles based on plasma OC and Hcy levels; fasting serum glucose varied inversely with OC but directly with Hcy tertiles (p=0.049, p=0.033 respectively). Atherogenic Index of Plasma (AIP=Log TG/HDL) predicts that diabetic patients with 36% high and 15% intermediate cardiovascular risk had increased frequency of low OC levels compared to low-risk patients (p=0.047). Another group of diabetic patients with 39% high and 11% intermediate CVD risk had increased frequency of high Hcy levels (p=0.033). A significant negative correlation existed between OC and glucose (r = -0.318; p = 0.035) while correlation between glucose level and Hcy (r = 0.851 p=0.022) was positive. Hence, low serum OC levels and high Hcy levels were associated with impaired glucose metabolism that may increase cardiovascular risk in DMII.

Keywords: osteocalcin, homocysteine, type 2 diabetes, cardiovascular

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Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: H. Haseena Banu, D. Karthick, R. Stalin, E. Nandha Kumar, T. P. Sachidanandam, P. Shanthi

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Background of the study: Type 2 diabetes is emerging as the predominant metabolic disorder in the world among adults characterized mainly by the resistance of the insulin sensitive tissues towards insulin followed by the decrease in the insulin secretion. The treatment for this disease usually involves treatment with oral synthetic drugs which are known to cause several side effects. Therefore, identification of new biomarkers as therapeutic target is the need of the hour. miRNAs are small, non–protein-coding RNAs that negatively regulate gene expression by promoting degradation and/or inhibit the translation of target mRNAs and have emerged as biomarkers in predicting diabetes mellitus. Objective of the study: To elucidate the therapeutic role of gallic acid in modulating the alterations in glucose metabolism induced by miRNAs 194 and 135a in Type 2 diabetic rats. Materials and Methods: T2D was induced in rats by feeding them with a high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg/body weight (b.wt.) of streptozotocin. Microarrays were used to assess the expression of miRNAs in control, diabetic and gallic acid treated rats. Gene expression studies were carried out by RT PCR analysis. Results: Forty one miRNAs were differentially expressed in Type 2 diabetic rats. Among these, the expression of miRNA 194 was significantly decreased whereas miRNA 135a was significantly increased in Type 2 diabetic rats. The glucose metabolism was also altered significantly in skeletal muscle of Type 2 diabetic rats. Conclusion: T2D is associated with alterations in the expression of miRNAs in skeletal muscle. Both these miRNAs 194 and 135a play an important role in glucose metabolism in skeletal muscle of diabetic rats. Gallic acid effectively ameliorated the alterations in glucose metabolism. Hence, both these miRNAs can serve as biomarkers and therapeutic targets in diabetes mellitus. The study also establishes the role of gallic acid as therapeutic agent. Acknowledgment: The financial assistance provided in the form of ICMR women scientist by ICMR DHR INDIA is gratefully acknowledged here.

Keywords: gallic acid, high fat diet, type 2 diabetes mellitus, miRNAs

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Authors: Yusuf U. Datti

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It is becoming increasingly clear that the consumption of resources now enjoyed in the developed nations will be impossible to be sustained worldwide. While developing countries still have the advantage of low consumption and a smaller ecological footprint per person, they cannot simply develop in the same way as other western cities have developed in the past. The severe reality of population and consumption inequalities makes it contentious whether studies done in developed countries can be translated and applied to developing countries. Additional to this disparities, there are few or no metabolism of energy studies in Nigeria. Rather more contentious majority of energy metabolism studies have been done only in developed countries. While researches in Nigeria concentrate on other aspects/principles of sustainability such as water supply, sewage disposal, energy supply, energy efficiency, waste disposal, etc., which will not accurately capture the environmental impact of energy flow in Nigeria, this research will set itself apart by examining the flow of energy in Nigeria and the impact that the flow will have on the environment. The aim of the study is to examine and quantify the metabolic flows of energy in Nigeria and its corresponding environmental impact. The study will quantify the level and pattern of energy inflow and the outflow of greenhouse emissions in Nigeria. This study will describe measures to address the impact of existing energy sources and suggest alternative renewable energy sources in Nigeria that will lower the emission of greenhouse gas emissions. This study will investigate the metabolism of energy in Nigeria through a three-part methodology. The first step involved selecting and defining the study area and some variables that would affect the output of the energy (time of the year, stability of the country, income level, literacy rate and population). The second step involves analyzing, categorizing and quantifying the amount of energy generated by the various energy sources in the country. The third step involves analyzing what effect the variables would have on the environment. To ensure a representative sample of the study area, Africa’s most populous country, with economy that is the second biggest and that is among the top largest oil producing countries in the world is selected. This is due to the understanding that countries with large economy and dense populations are ideal places to examine sustainability strategies; hence, the choice of Nigeria for the study. National data will be utilized unless where such data cannot be found, then local data will be employed which will be aggregated to reflect the national situation. The outcome of the study will help policy-makers better target energy conservation and efficiency programs and enables early identification and mitigation of any negative effects in the environment.

Keywords: built environment, energy metabolism, environmental impact, greenhouse gas emissions and sustainability

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Authors: Samir Malhotra, Rajan K. Khandotra, Rakesh K. Dhiman, Neelam Chadha

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There is paucity of data about safety and efficacy of probiotic treatment on patient outcomes in cirrhosis. Specifically, it is important to know whether probiotics can improve mortality, hepatic encephalopathy (HE), number of hospitalizations, ammonia levels, quality of life, and adverse events. Probiotics may improve outcomes in patients with acute or chronic HE. However, it is also important to know whether probiotics can prevent development of HE, even in situations where patients do not have acute HE at the time of administration. It is also important to know if probiotics are useful as primary prophylaxis of HE. We aimed to conduct an updated systematic review and meta-analysis to evaluate the safety and efficacy of probiotics in patients with cirrhosis. We searched PubMed, Cochrane library, Embase, Scopus, SCI, Google Scholar, conference proceedings, and references of included studies till June 2017 to identify randomised clinical trials comparing probiotics with other treatments in cirrhotics. Data was analyzed using MedCalc. Probiotics had no effect on mortality but significantly reduced HE (14 trials, 1073 patients, OR 0.371; 95% CI 0.282 to 0.489). There was not enough data to conduct a meta-analysis on outcomes like hospitalizations and quality of life. The effect on plasma ammonia levels was not significant (SMD -0.429; 95%CI -1.034 – 0.177). There was no difference in adverse events. To conclude, although the included studies had a high risk of bias, the available evidence does suggest a beneficial effect on HE. Larger studies with longer periods of follow-up are needed to determine if probiotics can reduce all-cause mortality.

Keywords: cirrhosis, hepatic encephalopathy, meta-analysis, probiotic

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Authors: Staniek Halina

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The inappropriate trace elements supply such as iron(III) and chromium(III) may be risk factors of many metabolic disorders (e.g., anemia, diabetes, as well cause toxic effect). However, little is known about their mutual interactions and their impact on these disturbances. The effects of Cr(III) supplementation with a deficit or excess supply of Fe(III) in vivo conditions are not known yet. The objective of the study was to investigate the combined effect of different Fe(III) levels in the diet and simultaneous Cr(III) supplementation on the Ca distribution in organs in healthy rats. The assessment was based on a two-factor (2x3) experiment carried out on 54 female Wistar rats (Rattus norvegicus). The animals were randomly divided into 9 groups and for 6 weeks, they were fed semi-purified diets AIN-93 with three different Fe(III) levels in the diet as a factor A [control (C) 45 mg/kg (100% Recommended Daily Allowance for rodents), deficient (D) 5 mg/kg (10% RDA), and oversupply (H) 180 mg/kg (400% RDA)]. The second factor (B) was the simultaneous dietary supplementation with Cr(III) at doses of 1, 50 and 500 mg/kg of the diet. Iron(III) citrate was the source of Fe(III). The complex of Cr(III) with propionic acid, also called Cr₃ or chromium(III) propionate (CrProp), was used as a source of Cr(III) in the diet. The Ca content of analysed samples (liver, kidneys, spleen, heart, and femur) was determined with the Atomic Absorption Spectrometry (AAS) method. It was found that different dietary Fe(III) supply as well as Cr(III) supplementation independently and in combination influenced Ca metabolism in healthy rats. Regardless of the supplementation of Cr(III), the oversupply of Fe(III) (180 mg/kg) decreased the Ca content in the liver and kidneys, while it increased the Ca saturation of bone tissue. High Cr(III) doses lowered the hepatic Ca content. Moreover, it tended to decrease the Ca content in the kidneys and heart, but this effect was not statistically significant. The combined effect of the experimental factors on the Ca content in the liver and the femur was observed. With the increase in the Fe(III) content in the diet, there was a decrease in the Ca level in the liver and an increase in bone saturation, and the additional Cr(III) supplementation intensified those effects. The study proved that the different Fe(III) content in the diet, independently and in combination with Cr(III) supplementation, affected the Ca distribution in organisms of healthy rats.

Keywords: calcium, chromium(III), iron(III), rats, supplementation

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Authors: Abdolamir Allameh, Shahnaz Esmaeili, Mina Allameh, Safoura Khajeniazi

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Stem cells with therapeutic applications can be isolated from human placenta/umblical cord blood (UCB) as well as the cord tissue (UC). Stem cells in culture are vulnerable to oxidative stress, particularly when subjected to differentiation process. The aim of this study was to examine the chnages in the rate of oxidation that occurs to cellular macromolecules during hepatic differentiation of mononuclear cells (MSCs). In addition, the impact of the hepatic differentiation process of MSC on cellular and biological activity of the cells will be undertaken. For this purpose, first mononuclear cells (MNCs) were isolated from human UCB which was obtained from a healthy full-term infant. The cells were cultured at a density of 3×10⁵ cells/cm² in DMEM- low-glucose culture media supplemented with 20% FBS, 2 mM L-glutamine, 100 μg/ml streptomycin and 100 U/ml penicillin. Cell cultures were then incubated at 37°C in a humidified 5% CO₂ incubator. After removing non-adherent cells by replacing culture medium, fibroblast-like adherent cells were resuspended in 0.25% trypsin-EDTA and plated in 25 cm² flasks (1×10⁴/ml). Characterization of the MSCs was routinely done by observing their morphology and growth curve. MSCs were subjected to a 2-step hepatocyte differentiation protocol in presence of hepatocyte growth factor (HGF), dexamethazone (DEX) and oncostatin M (OSM). The hepatocyte-like cells derived from MSCs were checked every week for 3 weeks for changes in lipid peroxidation, protein carbonyl formation and DNA oxidation i.e., 8-hydroxy-2'-deoxyguanosine (8-OH-dG) assay. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers such as albumin, was associated with increased levels of lipid peroxidation and protein carbonyl formation. Whereas, undifferentiated MSCs has relatively low levels of lipid peroxidation products. There was a significant increase ( p < 0.05) in lipid peroxidation products in hepatocytes on days 7, 14, and 21 of differentiation. Likewise, the level of protein carbonyls in the cells was elevated during the differentiation. The level of protein carbonyls measured in hepatocyte-like cells obtained 3 weeks after differentiation induction was estimated to be ~6 fold higher compared to cells recovered on day 7 of differentiation. On the contrary, there was a small but significant decrease in DNA damage marker (8-OH-dG) in hepatocytes recovered 3 weeks after differentiation onset. The level of 8-OHdG which was in consistent with formation of reactive oxygen species (ROS). In conclusion, this data suggest that despite the elevation in oxidation of lipid and protein molecules during hepatocyte development, the cells were normal in terms of DNA integrity, morphology, and biologically activity.

Keywords: adult stem cells, DNA integrity, free radicals, hepatic differentiation

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Authors: Natalia Moreno-Castellanos, Amaia Rodriguez, Gema Frühbeck

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Introduction: In adipocytes, the cytoskeleton undergoes important expression and distribution in adipocytes rearrangements during adipogenesis and in obesity. Indeed, a role for these proteins in the regulation of adipocyte differentiation and response to insulin has been demonstrated. Recently, septins have been considered as new components of the cytoskeletal network that interact with other cytoskeletal elements (actin and tubulin) profoundly modifying their dynamics. However, these proteins have not been characterized as yet in adipose tissue. In this work, were examined the cellular, molecular and functional features of a member of this family, septin 11 (SEPT11), in adipocytes and evaluated the impact of obesity on the expression of this protein in human adipose tissue. Methods: Adipose gene and protein expression levels of SEPT11 were analysed in human samples. SEPT11 distribution was evaluated by immunocytochemistry, electronic microscopy, and subcellular fractionation techniques. GST-pull down, immunoprecipitation and a Yeast-Two Hybrid (Y2H) screening were used to identify the SEPT11 interactome. Gene silencing was employed to assess the role of SEPT11 in the regulation of insulin signaling and lipid metabolism in adipocytes. Results: SEPT11 is expressed in human adipocytes, and its levels increased in both omental and subcutaneous adipose tissue in obesity, with SEPT11 mRNA content positively correlating with parameters of insulin resistance in subcutaneous fat. In non-stimulated adipocytes, SEPT11 immunoreactivity showed a ring-like distribution at the cell surface and associated to caveolae. Biochemical analyses showed that SEPT11 interacted with the main component of caveolae, caveolin-1 (CAV1) as well as with the fatty acid-binding protein, FABP5. Notably, the three proteins redistributed and co-localized at the surface of lipid droplets upon exposure of adipocytes to oleate. In this line, SEPT11 silencing in 3T3-L1 adipocytes impaired insulin signaling and decreased insulin-induced lipogenesis. Conclusions: Those findings demonstrate that SEPT11 is a novel component of the adipocyte cytoskeleton that plays an important role in the regulation of lipid traffic, metabolism and can thus represent a potential biomarker of insulin resistance in obesity in adipocytes through its interaction with both CAV1 and FABP5.

Keywords: caveolae, lipid metabolism, obesity, septins

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Authors: Tabassum Yasmin, Hamid Pahlevan

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HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

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Authors: Hafiz Arbab Sakandar

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Time-restricted intermittent fasting (TRIF) impacts host’s physiology and health. Plenty of health benefits have been reported for TRIF in animal models. However, limited studies have been conducted on humans especially in underdeveloped economies. Here, we designed a study to investigate the impact of TRIF/Ramadan fasting (16:8) on the modulation of gut-microbiome structure, metabolic pathways, and predicted metabolites and explored the correlation among them at different time points (during and after the month of Ramadan) in Pakistani Expats living in China. We observed different trends of Shannon-Wiener index in different subjects; however, all subjects showed substantial change in bacterial diversity with the progression of TRIF. Moreover, the changes in gut microbial structure by the end of TRIF were higher vis-a-vis in the beginning, significant difference was observed among individuals. Additionally, metabolic pathways analysis revealed that amino acid, carbohydrate and energy metabolism, glycan biosynthesis metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short chain fatty acid showed substantial difference at different time points based on the predicted metabolism. In conclusion, these results contribute to further our understanding about the key relationship among, dietary intervention (TRIF), gut microbiome structure and function. The preliminary results from study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome-tailored interventions among the Pakistani populace. Nonetheless, extensive, and rigorous large-scale research on the Pakistani population is necessary to expound on the association between diet, gut microbiome, and overall health.

Keywords: gut microbiome, health, fasting, functionality

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Authors: Caio E. G. Reis, Sara Wassell, Adriana L. Porto, Angélica A. Amato, Leslie J. C. Bluck, Teresa H. M. da Costa

Abstract:

Background: Multiple epidemiologic studies have consistently reported association between increased coffee consumption and a lowered risk of Type 2 Diabetes Mellitus. However, the mechanisms behind this finding have not been fully elucidated. Objective: We investigate the effect of coffee (caffeinated and decaffeinated) on glucose effectiveness and insulin sensitivity using the stable isotope minimal model protocol with oral glucose administration in healthy men. Design: Fifteen healthy men underwent 5 arms randomized crossover single-blinding (researchers) clinical trial. They consumed decaffeinated coffee, caffeinated coffee (with and without sugar), and controls – water (with and without sugar) followed 1 hour by an oral glucose tolerance test (75 g of available carbohydrate) with intravenous labeled dosing interpreted by the two compartment minimal model (225 minutes). One-way ANOVA with Bonferroni adjustment were used to compare the effects of the tested beverages on glucose metabolism parameters. Results: Decaffeinated coffee resulted in 29% and 85% higher insulin sensitivity compared with caffeinated coffee and water, respectively, and the caffeinated coffee showed 15% and 60% higher glucose effectiveness compared with decaffeinated coffee and water, respectively. However, these differences were not significant (p > 0.10). In overall analyze (0 – 225 min) there were no significant differences on glucose effectiveness, insulin sensitivity, and glucose and insulin area under the curve between the groups. The beneficial effects of coffee did not seem to act in the short-term (hours) on glucose metabolism parameters mainly on insulin sensitivity indices. The benefits of coffee consumption occur in the long-term (years) as has been shown in the reduction of Type 2 Diabetes Mellitus risk in epidemiological studies. The clinical relevance of the present findings is that there is no need to avoid coffee as the drink choice for healthy people. Conclusions: The findings of this study demonstrate that the consumption of caffeinated and decaffeinated coffee with or without sugar has no acute effects on glucose metabolism in healthy men. Further researches, including long-term interventional studies, are needed to fully elucidate the mechanisms behind the coffee effects on reduced risk for Type 2 Diabetes Mellitus.

Keywords: coffee, diabetes mellitus type 2, glucose, insulin

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Authors: Tugba Sevinc Gamsiz, Emine Koroglu, Ozcan Keskin

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Aim: Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease in the general population. The higher mortality and morbidity among NAFLD patients and lack of symptoms makes early detection and management important. In our study, we aimed to evaluate the relationship between noninvasive imaging and biochemical markers in diabetic and nondiabetic patients diagnosed with NAFLD. Materials and Methods: The study was conducted from (September 2017) to (December 2017) on adults admitted to Internal Medicine and Gastroenterology outpatient clinics with hepatic steatosis reported on ultrasound or transient elastography within the last six months that exclude patients with other liver diseases or alcohol abuse. The data were collected and analyzed retrospectively. Number cruncher statistical system (NCSS) 2007 program was used for statistical analysis. Results: 116 patients were included in this study. Diabetic patients compared to nondiabetics had significantly higher Controlled Attenuation Parameter (CAP), Liver Stiffness Measurement (LSM) and fibrosis values. Also, hypertension, hepatomegaly, high BMI, hypertriglyceridemia, hyperglycemia, high A1c, and hyperuricemia were found to be risk factors for NAFLD progression to fibrosis. Advanced fibrosis (F3, F4) was present in 18,6 % of all our patients; 35,8 % of diabetic and 5,7 % of nondiabetic patients diagnosed with hepatic steatosis. Conclusion: Transient elastography is now used in daily clinical practice as an accurate noninvasive tool during follow-up of patients with fatty liver. Early diagnosis of the stage of liver fibrosis improves the monitoring and management of patients, especially in those with metabolic syndrome criteria.

Keywords: diabetes, elastography, fatty liver, fibrosis, metabolic syndrome

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Authors: Hazha Hidayat, Shayma Ibrahim

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Folate metabolism plays a crucial role in the normal development of the neonatal central nervous system. It is regulated by MTHFR gene polymorphism. Any factors, which will affect this metabolism either by hereditary or gene mutation will lead to many mental disorders. The purpose of this study was to investigate whether MTHFR gene mutation contributes to the development of mental retardation and CP combined with mental retardation in Erbil city. DNA was isolated from the peripheral blood samples of 40 cases suffering from mental retardation (MR) and CP combined with MR were recruited, sequence the 4, 6, 7, 8 exons of the MTHFR gene were done to identify the variants. Exons were amplified by PCR technique and then sequenced according to Sanger method to show the differences with MTHFR reference sequences. We observed (14) mutations in 4, 6, 7, 8 exons in the MTHFR gene associated with Cerebral Palsy combined with mental retardation included deletion, insertion, Substitution. The current study provides additional evidence that multiple variations in the MTHFR gene are associated with mental retardation and Cerebral Palsy.

Keywords: methylenetetrahydrofolate reductase (MTHFR) gene, SNPs, homocysteine, sequencing

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Authors: Solange Adechian, Michèle Balage, Didier Remond, Carole Migné, Annie Quignard-Boulangé, Agnès Marset-Baglieri, Sylvie Rousset, Yves Boirie, Claire Gaudichon, Dominique Dardevet, Laurent Mosoni

Abstract:

Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, = whey) pulse, and MSP spread (n = 10-11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 ± 0.4 kg of weight, 5.1 ± 0.2 kg of fat, and 2.2 ± 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment.

Keywords: lean body mass, fat mass, casein, whey, protein metabolism

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Authors: Hai-Ying Liu, Yi-Hao Chen, Shu-Yin Pang, Feng-Hua Wang, Xiao-Fang Peng, Li-Yuan Yang, Zheng-Rong Chen, Yi Chen, Bing Zhu

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Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

Keywords: biliary atresia, liver fibrosis, MicroRNA, epithelial-mesenchymal transition, zinc finger E-box-binding homeobox 1

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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