Biochemistry and Molecular Biology Unit

Tunis, Tunisia

Biochemistry and Molecular Biology Unit

Tunis, Tunisia
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Demily C.,University of Lyon | Demily C.,National Reference Center for Wilsons disease | Parant F.,Biochemistry and Molecular Biology Unit | Broussolle E.,National Reference Center for Wilsons disease | And 7 more authors.
Annals of General Psychiatry | Year: 2017

Background: Wilson's disease (WD) is a rare autosomal-recessive, inherited disorder caused by a mutation in the copper-transporting gene ATP7B affecting the liver and nervous system. About 30% of patients with WD may initially present with psychiatric symptoms, and diagnosis can be difficult to establish. The objectives of the present preliminary study were [1] to evaluate the relevance of serum copper (Cu) and ceruloplasmin (Cp) measures in hospitalized patients with psychiatric disorders; and [2] to identify possible mutations in the ATP7B gene in patients with abnormal biological copper profile. Methods: All psychiatric patients who participated in this study were hospitalized in Saint-Jean de Dieu Hospital (Lyon, France). Cp was measured by immunoturbidimetry and serum Cu by inductively coupled plasma-optical emission spectrometry. When Cp and serum Cu levels were inferior to, respectively, 0.18 g/L and 0.88 mg/L in combination with atypical psychiatric presentations, complete clinical examinations were performed by multidisciplinary physicians specialized in WD. In addition, mutation detection in the ATP7B gene was performed. Results: A total of 269 patients completed the study. (1) 51 cases (19%) showed both decreased Cp and Cu concentrations. (2) Molecular genetic tests were performed in 29 patients, and one ATP7B mutation (heterozygous state) was found in four patients. We identified three different missense mutations: p.His1069Gln, c.3207C>A (exon 14), p.Pro1379Ser, c.4135C>T (exon 21) and p.Thr1434Met, c.4301C>T (exon 21). No pathogenic mutation on either ATP7B allele was detected. Conclusion: Results of Cp and/or serum Cu concentrations below the normal limits are common in patients with psychiatric disorders and nonrelevant and/or informative for the WD diagnosis. WD diagnosis is based on a combination of clinical and biological arguments. Psychiatric patients with suspicion of WD should be evaluated in a reference center. Trial registration CPP Lyon Sud-Est IVNo 10/044, CNIL No DR-2011-470, Afssaps No B100832-40 and CCTIRS No 10.612 bis, registered 8 June 2010 © 2017 The Author(s).


Tambo E.,Biochemistry and Molecular Biology Unit | Fouad A.M.,Biochemistry and Molecular Biology Unit | Khater E.I.M.,Biochemistry and Molecular Biology Unit | Khater E.I.M.,Ain Shams University
International Journal of Emergency Management | Year: 2017

Background: Increasing natural and man-made threats to communities and disaster vulnerabilities have been linked to globalisation, increasing urbanisation and climate changes. This review paper analyses the changing trend and pattern in natural and man-made evolving emergencies threats and disasters vulnerability, towards robust and effective emergency community-based preparedness, emergency response policy and programs in Saudi Arabia. Method: A systematic review was performed to assess community emergency readiness in man-made or natural threats and epidemics disasters in the Kingdom. Findings: Our results showed that man-made disasters were the most reported cause of fatality with over 3979 deaths from 1975 to April, 2016. Substantially, Saudi Arabia government commitment and investment efforts have been devoted to ensure adequate emergency management. However, the level of community emergency preparedness culture for all types of risk assessment and management still requires urgent attention in the context of emerging global health threats and epidemics. This paper provides a set of lessons learnt that are useful to foster and scale-up further policy-makers and emergency planners proactive emergency preparedness capacity, and communities resilience initiatives. Leveraging on aggregate annual Hajj and Umrah pilgrimage or mass gathering lessons learnt, global emergency response experiences and best practices are assets in scaling-up proactive and practical community/public and regional emergency security resilience. Conclusion: Strengthening evidence-based comprehensive sustained Saudi innovative community-based emergency partnerships, community surveillance and preparedness, resilient measures and best practices against threats and disasters is advocated. Copyright © 2017 Inderscience Enterprises Ltd.


Cornen S.,Institute Paoli Calmettes IPC | Guille A.,Institute Paoli Calmettes IPC | Adelaide J.,Institute Paoli Calmettes IPC | Addou-Klouche L.,Institute Paoli Calmettes IPC | And 21 more authors.
PLoS ONE | Year: 2014

Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype. © 2014 Cornen et al.


PubMed | Sidra Medical and Research Center, Biochemistry and Molecular Biology Unit and Harvard University
Type: | Journal: Scientific reports | Year: 2015

Betatrophin/ANGPTL8 is a newly identified hormone produced in liver and adipose tissue that has been shown to be induced as a result of insulin resistance and regulates lipid metabolism. Little is known about betatrophin level in humans and its association with T2D and metabolic risk factors. Plasma level of betatrophin was measured by ELISA in 1603 subjects: 1047 non-diabetic and 556 T2D subjects and its associations with metabolic risk factors in both non-diabetic and T2D were also studied. Our data show a significant difference in betatrophin levels between non-diabetic (731.3 (59.5-10625.0) pg/ml) and T2D (1710.5 (197.4-12361.1) p < 0.001. Betatrophin was positively correlated with age, BMI, waist/hip ratio, FBG, HbA1C, HOMA-IR and TG in the non-diabetic subjects. However, no association was observed with BMI, FBG, HbA1C or HOMA-IR in T2D subjects. TC and LDL showed negative association with betatrophin in T2D subjects. Multivariate analysis showed that subjects in the highest tertile of betatrophin had higher odds of having T2D (odd ratio [OR] = 6.15, 95% confidence interval [CI]=(3.15 - 12.01). Our data show strong positive associations between betatrophin and FBG and insulin resistance in non-diabetic subjects. However, correlations with FBG and insulin resistance were diminished in T2D subjects.


Abu-Farha M.,Biochemistry and Molecular Biology Unit | Abubaker J.,Biochemistry and Molecular Biology Unit | Al-Khairi I.,Biochemistry and Molecular Biology Unit | Cherian P.,Biochemistry and Molecular Biology Unit | And 7 more authors.
Cardiovascular Diabetology | Year: 2016

Background: ANGPTL8 also called betatrophin is a regulator of lipid metabolism through its interaction with ANGPTL3. It has also been suggested to play a role in insulin resistance and beta-cell proliferation. Based on its function, we hypothesized that ANGPTL8 will play a role in Metabolic Syndrome (MetS). To test this hypothesis we designed this study to measure ANGPTL8 level in subjects with MetS as well as its association with high sensitivity C-reactive protein (HsCRP) level in humans. Methods: ANGPTL8 level was measured using ELISA in subjects with MetS as well as their controls, a total of 1735 subjects were enrolled. HsCRP was also measured and its association with ANGPTL8 was examined. Results: ANGPTL8 level was higher in subjects with MetS 1140.6 (171.9-11736.1) pg/mL compared to 710.5 (59.5-11597.2) pg/mL in the controls. Higher levels of ANGPTL8 were also observed with the sequential increase in the number of MetS components (p value = <0.0001). ANGPTL8 showed strong positive correlation with HsCRP (r = 0.15, p value = <0.0001). Stratifying the population into tertiles according to the level of HsCRP showed increased ANGPTL8 level at higher tertiles of HsCRP in the overall population (p value = <0.0001).A similar trend was also observed in MetS and non-MetS subjects as well as in non-obese and obese subjects. Finally, multiple logistic regression models adjusted for age, gender, ethnicity and HsCRP level showed that subjects in the highest tertiles of ANGPTL8 had higher odds of having MetS (odd ratio [OR] = 2.3, 95 % confidence interval [CI] = (1.6-3.1), p value <0.0001. Conclusion: In this study we showed that ANGPTL8 is increased in subjects with MetS and it was significantly associated with HsCRP levels in different subgroups highlighting its potential role in metabolic and inflammatory pathways. © 2016 Abu-Farha et al.


PubMed | Dasman Diabetes Institute, Biochemistry and Molecular Biology Unit and Sidra Medical and Research Center
Type: | Journal: Cardiovascular diabetology | Year: 2016

ANGPTL8 also called betatrophin is a regulator of lipid metabolism through its interaction with ANGPTL3. It has also been suggested to play a role in insulin resistance and beta-cell proliferation. Based on its function, we hypothesized that ANGPTL8 will play a role in Metabolic Syndrome (MetS). To test this hypothesis we designed this study to measure ANGPTL8 level in subjects with MetS as well as its association with high sensitivity C-reactive protein (HsCRP) level in humans.ANGPTL8 level was measured using ELISA in subjects with MetS as well as their controls, a total of 1735 subjects were enrolled. HsCRP was also measured and its association with ANGPTL8 was examined.ANGPTL8 level was higher in subjects with MetS 1140.6 (171.9-11736.1) pg/mL compared to 710.5 (59.5-11597.2) pg/mL in the controls. Higher levels of ANGPTL8 were also observed with the sequential increase in the number of MetS components (p value = <0.0001). ANGPTL8 showed strong positive correlation with HsCRP (r = 0.15, p value = <0.0001). Stratifying the population into tertiles according to the level of HsCRP showed increased ANGPTL8 level at higher tertiles of HsCRP in the overall population (p value = <0.0001).A similar trend was also observed in MetS and non-MetS subjects as well as in non-obese and obese subjects. Finally, multiple logistic regression models adjusted for age, gender, ethnicity and HsCRP level showed that subjects in the highest tertiles of ANGPTL8 had higher odds of having MetS (odd ratio [OR] = 2.3, 95 % confidence interval [CI] = (1.6-3.1), p value <0.0001.In this study we showed that ANGPTL8 is increased in subjects with MetS and it was significantly associated with HsCRP levels in different subgroups highlighting its potential role in metabolic and inflammatory pathways.

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