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It has been previously shown that clinical cardiovascular manifestations can be caused by mild changes in thyroid function. However, the implication of angiotensinogen (Agt) and vascular smooth muscle cells (VSMCs) dysfunction in the pathophysiology of cardiovascular manifestations in hypothyroidism have not yet been investigated. We induced experimental hypothyroidism in Psammomys obesus by administering carbimazole for five months. At the end of the experiment, the animals were sacrificed and histopathological analysis was performed using Masson's trichrome staining of the aorta and thyroid gland. The expression of the Agt gene and the genes implicated in cholesterol metabolism regulation in the liver and VSMCs was determined by qRT-PCR. Histological observations revealed profound remodeling of the aorta structure in animals with hypothyroidism. In addition, Agt gene expression in the liver was significantly increased. In vitro study, showed that VSMCs from hypothyroid animals overexpressed 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and Acyl CoA:cholesterol acyltransferase (Acat) 1, with failure to increase the efflux pathway genes (ATP-binding cassette subfamily G member (Abcg) 1 and 4). These results suggest that hypothyroidism leads to vascular alterations, including structural remodeling, VSMCs cholesterol metabolism dysfunction, and their switch to a synthetic phenotype, together with hepatic Agt gene overexpression., (© 2023. The Author(s).)

Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis (RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated either with melatonin (10 mg/kg body weight (BW)/24 h) (M-ZDF and M-ZL) or non-treated (control) (C-ZDF and C-ZL) for 12 weeks. Western blot analysis showed that mitochondrial fission, fusion, and autophagy were altered in the C-ZDF group, accompanied by reduced SIRT1 levels. Furthermore, C-ZDF rats exhibited depleted ATP production and nitro-oxidative stress, as indicated by increased nitrites levels and reduced SOD activity. Western blotting of MyH isoforms demonstrated a significant decrease in both slow and fast oxidative fiber-specific markers expression in the C-ZDF group, concomitant with an increase in the fast glycolytic fiber markers. At the tissue level, marked fiber atrophy, less oxidative fibers, and excessive lipid deposition were noted in the C-ZDF group. Interestingly, melatonin treatment partially restored mitochondrial fission/fusion imbalance in the RVL muscle by enhancing the expression of fission (Fis1 and DRP1) markers and decreasing that of fusion (OPA1 and Mfn2) markers. It was also found to restore autophagy, as indicated by increased p62 protein level and LC3BII/I ratio. In addition, melatonin treatment increased SIRT1 protein level, mitochondrial ATP production, and SOD activity and decreased nitrites production. These effects were associated with enhanced oxidative phenotype, as evidenced by amplified oxidative fiber-specific markers expression, histochemical reaction for NADH enzyme, and muscular lipid content. In this study, we showed that melatonin might have potential therapeutic implications for obesity-induced SKM metabolic inflexibility among patients with obesity and T2DM.

Experimental data have revealed that melatonin at high doses reduced obesity and improved metabolic outcomes in experimental models of obesity, mainly by enhancing brown adipose tissue (BAT) thermogenesis. A potential dose-response relationship has yet to be performed to translate these promising findings into potential clinical therapy. This study aimed to assess the effects of different doses of melatonin on interscapular BAT (iBAT) thermogenic capacity in Zücker diabetic fatty (ZDF) rats. At 6 wk of age, male ZDF rats were divided into four groups ( n = 4 per group): control and those treated with different doses of melatonin (0.1, 1, and 10 mg/kg of body weight) in their drinking water for 6 wk. Body weight (BW) was significantly decreased at doses of 1 and 10 mg/kg of melatonin, but not at 0.1 mg/kg compared with the control, with a similar rate of BW decrease being reached at the dose of 1 mg/kg (by ~11%) and 10 mg/kg (by ~12%). This effect was associated with a dose-dependent increase in the thermal response to the baseline condition or acute cold challenge in the interscapular area measurable by infrared thermography, with the highest thermal response being recorded at the 10 mg/kg dose. Upon histology, melatonin treatment markedly restored the typical brownish appearance of the tissue and promoted a shift in size distribution toward smaller adipocytes in a dose-dependent fashion, with the most pronounced brownish phenotype being observed at 10 mg/kg of melatonin. As a hallmark of thermogenesis, the protein level of uncoupled protein 1 (UCP1) from immunofluorescence and Western blot analysis increased significantly and dose-dependently at all three doses of melatonin, reaching the highest level at the dose of 10 mg/kg. Likewise, all three doses of melatonin modulated iBAT mitochondrial dynamics by increasing protein expression of the optic atrophy protein type 1 (OPA1) fusion marker and decreasing that of the dynamin-related protein1 (DRP1) fission marker, again dose-dependently, with the highest and lowest expression levels, respectively, being reached at the 10 mg/kg dose. These findings highlight for the first time the relevance of the dose-dependency of melatonin toward BW control and BAT thermogenic activation, which may have potential therapeutic implications for the treatment of obesity. To clinically apply the potential therapeutic of melatonin for obesity, we consider that the effective animal doses that should be extrapolated to obese individuals may be within the dose range of 1 to 10 mg/kg.

Introduction: Cardiovascular diseases were defined as coronary artery, cerebrovascular, or peripheral arterial disease. Hyperhomocysteinemia (Hhcy) is an independent risk factor of cardiovascular diseases, including atherosclerosis. Our previous studies demonstrated the involvement of Hhcy in cardiovascular remodeling in the sand rat Psammomys obesus., Material and Methods: An experimental Hhcy was induced, in the sand rat Psammomys obesus, by a daily intraperitoneal injection of 70 mg/kg of methionine for a total duration of 6 months. The impact of Hhcy on the cellular and matrix structures of the heart, aorta and liver was analyzed using histological techniques. Additionally we treatedprimary cultures of aortic smooth muscle cells (SMCs) with high concentration of methionine to investigate the effects of methionine at the cellular level., Results: A moderate Hhcy induced a significant increase in the extracellular matrix components particularly collagens which accumulated in the interstitial and perivascular spaces in the studied organs indicating a developing fibrosis. A liver steatosis was also observed following methionine treatment. Further analysis of the aorta showed that Hhcy also induced vascular alterations including SMCs reorientation and proliferation associated with aneurysm formation., Conclusions: Our results show for the first time that Hhcy can induce a cardiovascular and liver diseases phenotype in Psammomys obesus, a species previously shown to be a good model for the studies of diabetes and other metabolism-related pathologies.

Background: Lipotoxicity is characterized by a metabolic disturbance leading to the development of nonalcoholic fatty liver disease (NAFLD). Some medicinal plant extracts exert hepatoprotective activity by modulating oxidative stress, inflammation, and metabolic disorders. Scolymus hispanicus or the golden thistle can be considered an important natural source of antioxidants. In traditional medicine, the consumption of this plant is recommended for diseases of the liver and intestines., Objective: In this study, we aimed to determine the effects of Scolymus hispanicus on a hyperfatty diet- (HFD-) induced metabolic disorders, oxidative stress, and inflammation., Materials and Methods: Our experiment focused on the administration of an HFD (40%) in Rattus norvegicus for 2 months and treatment with the aqueous extract of Scolymus hispanicus at a rate of 100 mg/kg during the last eight days of experimentation. In this context, several aspects were studied: the evaluation of blood biochemical parameters, liver function such as lipids and glycogen, markers of oxidative stress (TBARS, carbonyl proteins, advanced oxidation proteins, catalase, and SOD) and inflammation (NO and NFkB), morphological study of hepatocytes in primary culture, and histological study of the liver., Results: Lipotoxicity induced metabolic disorders, both serum and tissue. HFD induced an increase in the total lipids and a decrease in glycogen reserve and an alteration in the oxidant-antioxidant balance. HFD induced an increase in markers of liver damage, which resulted in NAFLD, confirmed by histological study and hepatocytes cell culture. Scolymus appears to have lipid-lowering, hypoglycemic, anti-inflammatory and antioxidant properties. It improved glucose tolerance and the condition of fatty liver disease., Conclusion: Golden thistle improves glucose tolerance and hyperlipidemia and ameliorates hepatic steatosis by reducing oxidative stress, inflammation, and lipid accumulation. Its incorporation into a dietary program or as an aliment supplement would prevent hepatic complications associated with an HFD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Sihem Berdja et al.)

Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that the renoprotective effect of melatonin administration was associated with restoring mitochondrial fission/fusion balance and function in a rat model of diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight (BW)/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Western blot analysis of ER stress-related markers and renal morphology were assessed. Compared to C-ZL rats, higher ER stress response associated with impaired renal morphology was observed in C-ZDF rats. Melatonin supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect on phospho-protein kinase RNA-like endoplasmic reticulum kinase (PERK) level. In addition, melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins phospho-c-jun amino terminal kinase (JNK), Bax, and cleaved caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were associated with renal structural recovery. Taken together, our findings revealed that melatonin play a renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK signaling pathway.

Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolicoutcomes in several animal models of obesity. However, there is, as of yet, scarce evidence concerning its effectiveness against obesogenic challenges that more accurately mimic human Western diets, such as the cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in a cafeteria-diet-induced obesity model. Male Wistar rats were fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks and were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 h per day. Rats under the TRF regimen had a lower body weight gain and adiposity than the diet-matchedad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile (total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c)) and atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), coronary risk index (CRI) in CAF-fed rats. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), were also up-regulated in the iWAToftime-restricted NC- or CAF-fed rats. These findings suggest that a TRF regimen is an effective strategy to improve CAF diet-induced obesity, probably via a mechanismthe involving WAT browning process.

The aim of this study is to evaluate the anomalies of coagulation (by assaying the factor VIII, fibrinogen, D-dimer and resistance to activated protein C) in patients with lung cancer., Methods: 101 patients newly diagnosed with lung cancer before treatment and 72 control blood donors were included in the study after informed consent. All coagulation tests were performed on Stago STA-Compact. Statistical analyses were performed using the SPSS software version 22., Results: The study of the coagulation showed that plasma levels of all coagulation parameters were significantly higher in patients compared to controls. Coagulation was not influenced by the age of patients. No significant difference was found between the histological types in terms of coagulation. Factor VIII level was significantly elevated in stage IV patients compared to stage I + II + III patients. At the cut-off value of 6.22 g/L, the elevation of fibrinogen had a significant statistical relationship with thromboembolic disease (p=0.014) giving an hazard ratio of 3.868, confidence interval [1.358-11.012]. In multivariate analysis the hazard ratio doubled to 6.398, confidence interval [1,970-20,778]., Discussion: Lung cancer patients showed an increase in coagulation factors that resulted in a state of hypercoagulability that was independent of the histology of lung cancer. The elevation of fibrinogen was predictive of thromboembolic disease at the early diagnosis of lung cancer before any therapy.

Objectives: The tissue renin-angiotensin system (tRAS) plays a key role in the maintenance of cellular homeostasis but is also implicated in atherosclerosis. Thyroid hormone (TH) contributes, via genomic effects, to control of tRAS gene expression in the arterial wall and vascular smooth muscle cells (VSMCs). We investigated the specific functions of TH receptors-α and -β (TRα and TRβ) on tRAS gene expression in the aorta and VSMCs, and the potential protective effect of TRα against atherosclerosis., Material and Methods: Using aorta and cultured aortic VSMCs from TRα and TRβ deficient mice, tRAS gene expression was analyzed by determining mRNA levels on real-time PCR. Gene regulation under cholesterol loading mimicking atherosclerosis conditions was also examined in VSMCs in vitro., Results: TRα deletion significantly increased expression of angiotensinogen (AGT) and angiotensin II receptor type 1 subtype a (AT 1 R a ) at transcriptional level in aorta, a tissue with high TRα expression level. TRα activity thus seems to be required for maintenance of physiological levels of AGTand AT 1 R a expression in the arterial wall. In addition, during cholesterol loading, TRα deletion significantly increased cholesterol content in VSMCs, with a weaker decrease in AGTexpression., Conclusion: TRα seems to have an inhibitory impact on AGTand AT 1 R a expression, and loss of TRα function in TRα 0/0 mice increases tRAS expression in the aortic wall. More importantly, TRα deletion significantly increases VSMC cholesterol content. Our results are consistent with a protective role of TRα against atherosclerosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Hypothesis: How are the epidemiologic repartition and the physiopathology of lung cancer (LC) in Algeria? Objective: Our study aimed to establish the clinico-epidemiological profile and evaluate redox imbalance in Algerian patients with LC. Methods and results: Our study concerned 94 Algerian patients with LC treated at two hospitals of Algiers, the capital of Algeria. The clinico-epidemiological profile was established. Moreover, the redox imbalance was evaluated by dosing oxidative stress (OS) parameters in tumor tissues and blood. We noted that the average age was 62.06 years, and 79 among the 94 patients were male, 94.59% of which were smokers. The most common histological type was adenocarcinoma (45.45% of cases), followed by squamous cell carcinoma (37.88%) small-cell carcinoma (4.86%) and other histological types (6.67%), while the most frequent clinical stage was IV (66.95 %). 23 of the 94 patients were exposed to particular risk factors such as masonry products, metal mechanics, coal smoke and so forth. In other respects, the OS parameters: NO (Nitrogen monoxide), AOPP (Advanced Oxidation Protein Products) and MDA (Malondialdehyde) were higher in tumor tissues compared to peritumoral stroma (control), unlike the catalase activity. Otherwise, AOPP and MDA were significantly higher in patients' blood than in healthy control blood, in contrast to the catalase activity. Discussion: The LC has a heterogeneous repartition regarding the sex, age, histological types, the smoking status and professional exposition to risk factors in the Algerian population. Moreover, the oxidative stress impacts the physiopathology of LC.

In our study, we propose to analyze the effects of resveratrol (RES) and quercetin (QRC) on proliferation markers, oxidative stress, apoptosis, and inflammation of aortic fibroblasts of Psammomys obesus after induced oxidative stress by hydrogen peroxide (H2O2). Fibroblasts were incubated in RES 375 μM and QRC 0.083 μM for 24 hours after exposure to H2O2 1.2 mM for 6 hours. We performed the proliferation rate, cells viability, morphological analyses, cytochrome c, Akt, ERK1/2, and p38 MAPK quantification. The redox status was achieved by proportioning of malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl proteins, catalase, and superoxide dismutase activity. The inflammation was measured by TNFα, MCP1, and NF-kB assay. The extracellular matrix (ECM) remodeling was performed by SDS-PAGE. Stressed fibroblasts showed a decrease of cell proliferation and viability, hypertrophy and oncosis, chromatin hypercondensation and increase of cytochrome c release characteristic of apoptosis, activation of ERK1/2 and Akt pathway, and decreases in p38 MAPK pathways marking the cellular resistance. The redox state was disrupted by increased malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl protein production, catalase and superoxide dismutase activity, and a decreased production of proteins including collagens. Inflammation state was marked by MCP-1, TNFα, and NF-kB increase. Treatment of fibroblasts stressed by RES and QRC inverted the oxidative stress situation decreasing apoptosis and inflammation, and improving the altered redox status and rearrangement of disorders observed in extracellular matrix. H2O2 induced biochemical and morphological alterations leading to apoptosis. An improved general condition is observed after treatment with RES and QRC; this explains the antioxidant and antiapoptotic effects of polyphenols.

The T300A variant is among the most Crohn's disease (CD) associated genetic variants. The aim of our study is to bring a first insight about the contribution of the T300A variant in a cohort of Algerian CD. In a case/control design, 118 Algerian CD patients and 161 unrelated healthy subjects were genotyped for the T300A variant using the allelic discrimination test by Applied Biosystems Taqman ® genotyping technology. A serological analysis was carried out using Biosystems™ ELISA kit for the assessment of the anti-Saccharomyces cerevisiae antibodies and immunofluorimetry via Luminex ® technology for the evaluation of cytokine levels (TNFα, IFNγ, IL-6 and IL-17). The comparison between allelic and genotypic frequencies was performed using the χ 2 test and the exact Fischer test. The odds ratio (OR) was noted adopting confidence interval of 95%. The comparison between the averages was carried out by the Mann-Whitney and Kruskal-Wallis tests. A factorial discriminant analysis and a binary logistic regression were performed as further analyses. The T300A variant showed an increased risk of CD within homozygous variant carriers (P=0.027). Moreover, the carriage of the G allele was associated with the early onset of CD (P=0.01) and a severe CD impairment (P=0.045). We were not able to comfort the association of the T300A variant and ASCA IgA, ASCA IgG and IFNγ levels detected at the univariate analysis. Our results suggest a possible association between the T300A variant and CD in this cohort of Algerian CD patients. Moreover, this variant might be incriminated in the early onset of CD and a severe disease impairment. At the serological study, the univariate and the multivariate analyses yielded contradictory results. Further investigations of larger cohorts of Algerian CD are needed to better assess the suggested associations at the present study., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The zinc transporter 8 (ZnT8) is an islet β-cell secretory granule membrane protein coded by the SLC30A8 gene, identified as a novel autoantigen in human type 1 diabetes (T1D). As no data of ZnT8ab in Algerian patients have been reported, we aim to evaluate the prevalence of ZnT8ab in young Algerians with T1D and determine whether ZnT8ab could be a better diagnostic tool to replace the other conventional autoantibodies detected in patients with type 1 diabetes. For this purpose, we evaluated the prevalence of islets cells antibodies (ICA), glutamic acid decarboxylase (GAD), islet antigen type 2 (IA2), insulin (IA) autoantibodies (ab) and for the first time in Algeria, the zinc transporter 8 (ZnT8) in young Algerian patients with type 1 diabetes., Patients and Methods: In our cross-sectional study, 160 patients between 1 and 35 years old, diagnosed with type 1 diabetes were enrolled. ICAab was analyzed by indirect immunofluorescence (IIF), GADab, IA2ab, IAab and ZnT8ab were analyzed by ELISA, fasting blood glucose was performed by enzymatic method (glucose-oxidase) and HbA1c by turbid metric method., Results: Our cohort was composed with 74 males and 86 females (OR=1.16); the mean of age was 14.09 [1-35] years old and the median diabetes duration was 4.10 [1-18] years. Our cohort had a mean of HbA1c of 9.22 [5.40-15]%, the mean of birth weight was 3360.52 [2200-4800]g; the mean of BMI was 19.30 [16.04-22.46]kg/m 2 . Out of 160 patients, 44 (27.5%) were under mother breastfeeding and 116/160 (72.5%) were under artificial feeding. One antibody, at least, was found in 94.38% and the ZnT8ab was significantly more positive in females (70.3%) than in males (10.7%) (***P=8.033×10 -15 ). The concentration of ZnT8ab was higher in females than in males (females=122.25UI/mL versus males=51.38UI/mL; *P=0.03); ICAab, GADab and ZnT8ab were more present in patients with consanguineous parents (***P=0.0002, *P=0.019 and *P=0.03; respectively) CONCLUSION: Our study on ZnT8ab in T1D is the first in the Maghreb region and we observed a prevalence of 46.25%. The positivity of ZnT8ab enabled us to classify in T1DA 50% of diabetics with obvious T1D phenotype and negative routine autoantibodies, thus ZnT8ab is a good tool for differential diagnosis of type 1 diabetes. According to our results, a simultaneous analysis for ZnT8 and IA2 autoantibodies can be a better and efficient diagnosis of type 1A diabetes from the beginning of the disease., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE-/- mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE-/- mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver. However, TRα deletion in the arterial wall suppressed the expression of genes involved in the esterification and excretion of cholesterol and enhanced the expression of angiotensinogen (AGT). The VSMCs of the ApoE-/- and DKO mice increased their cholesterol content during cholesterol loading, but failed to increase the expression of ATP-binding cassette transporter A1 (ABCA1). T3 addition partially corrected these abnormalities in the cells of the ApoE-/- mice but not those of the DKO mice. In conclusion, TRα deletion in ApoE-/- mice slightly increases the expression of tRAS in the aorta and aggravates the dysregulation of cholesterol content in the VSMCs., (© 2018 S. Karger AG, Basel.)

In atherosclerosis studies, there are few data, especially in men, on the biology of perivascular adipose tissue (PVAT) compared to that of other adipose tissue (AT), on amendments in obesity, and its possible role in the development of atherosclerosis. We conducted an ex vivo human study on pericarotid adipose tissue-collected in the immediate vicinity (PVATp) and away from the plate (tapas)-and subcutaneous (SC) neck gathered during surgery from patients suffering from atheromatous carotid disease. In addition, we conducted a study in obese Zucker rats (models of obesity and insulin resistance) and Wistar rats subjected to moderate stress. In these models, we collected renal adipose tissue (RAT), epididymal adipose tissue (EAT), and TAPA samples. On all samples, we measured mRNA levels encoding for proinflammatory cytokines (TNFα, IL-6, IL-1β, MCP-1). Our results showed an increase in mRNA MCP-1, TNF and IL-6 in the adipose tissue around atherosclerotic plaques, an increase that was greater in diabetics than in non-diabetic subjects; we noted for the mRNA of MCP-1 in the TAPAp, 3.49×10 -2 ±1.17×10 -2 ng/ug 18S in diabetic patients compared to 7.26×10 -3 ±1.00×10 -3 ng/ug 18S ( ** P<0.01) in non-diabetic patients. In the obese Zucker rat, we found a significant increase in IL-6 in TAPA in obese animals compared to the corresponding controls (4.24×10 -5 ±1.75×10 -6 ng/μg 18S vs 1.29×10 -5 ±1.55×10 -6 ng/ug 18S). In stressed rats, we recorded a TNFα mRNA increase in the PVAT and EAT in the stressed rats compared to fatty tissue of control animals, we note respectively, 7.52×10 -3 ±2.8×10 -3 ng/μg 18S vs 2.62×10 -3 ±0.57×10 -3 ng/18S and 4.78×10 -3 ±1.52×10 -3 ng/μg 18S vs 2.02×10 -3 ±0.3×10 -3 ng/ug 18S. In summary, our work shows an inflammatory state of the TAPA surrounding the atheromatous plaques in diabetic patients. An obesity or stress state promotes an inflammatory profile of PVAT., (Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM., Material and Methods: The study was conducted in 22 adult male Wistar rats. The rats were divided into two groups: a control group, which received standard diet and tap water; the treated group received the same diet and water supplemented with solution of L-methionine (200 mg/kg b.w./day) for 6 months. Plasma homocysteine concentration was measured. Histological changes were observed with light microscope. The presence of collagen I and III and metalloproteinases (2, 3, 7 and 9) in the seminal vesicles was examined using immunohistochemistry and Western blotting., Results: Plasma Hcy levels increased significantly after methionine treatment and interfered significantly with body weight in treated rats. The content of fibrillar collagens (I and III) in the wall of seminal vesicles was elevated in hyperhomocysteinemic rats. Moreover, we found that hyperhomocysteinemia increased the expression of MMP-2, -3, -7 and -9 in seminal vesicles of experimental rats., Conclusions: Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of MMPs in rat seminal vesicles might contribute to the remodeling of seminal vesicles.

Context. Nigella sativa seeds are usually used as traditional medicine for a wide range of therapeutic purposes. Objective. To investigate the subacute toxicity of NS aqueous extract and select its lowest dose to study its antidiabetic effect. Methods. 5 AqE.NS doses (2, 6.4, 21, 33, and 60 g/Kg) were daily administered to mice by gavage. Biochemical parameters measurements and histological study of the liver and the kidney were performed after 6 weeks of supplementation. Thereafter, and after inducing diabetes by alloxan, rats were treated by 2 g/Kg of AqE.NS during 8 weeks. Metabolic parameters were measured on sera. A horizontal electrophoresis of plasmatic lipoprotein was conducted. Glycogen, total lipids, and triglycerides were measured in the liver. TBARS were evaluated on adipose tissue, liver, and pancreas. Results. AqE.NS showed no variation in urea and albumin at the 5 doses, but hepatotoxicity from 21 g/Kg was confirmed by histopathological observations of the liver. In diabetic rats, AqE.NS significantly decreased glycemia, TG, T-cholesterol, LDL-c, and TBARS and showed a restored insulinemia and a significant increase in HDL-c. Results on the liver indicated a decrease in lipids and a possible glycogenogenesis. Conclusion. AqE.NS showed its safety at low doses and its evident antihyperglycemic, antihyperlipidemic, and antioxidant effect.

This study investigated whether a high Met diet influences biochemical parameters, MMPs activities in plasma, and biochemical and histological remodeling in aorta, in both pregnant female rabbits and their offspring. Four female rabbit groups are constituted (each n = 8), nonpregnant control (NPC), pregnant control (PC) that received normal commercial chow, nonpregnant Met (NPMet), and pregnant Met (PMet) that received the same diet supplemented with 0,35% L-methionine (w/w) for 3 months (500 mg/d). All pregnant females realize 3 successive pregnancies. Plasma results showed that Met excess increased Hcy, raised CRP in NPMet and decreased it in PMet, enhanced significantly proMMP-2 and proMMP-9 activities in NPMet, and reduced them in PMet. Aorta showed a rise in collagen level, essentially in PMet, a reduction of elastin content in both PMet and NPMet, and a significant decrease in lipid content in PMet, with histological changes that are more pronounced in NPMet than PMet. Met excess enhanced proMMP-9 activities in NPMet while it decreased them in PMet. PMet newborn presented increase in uremia and CRP and significant rise of active MMP-2 and MMP-9 forms. In aorta, media and adventitia thickness increased, total lipids content decreased, proMMP-9 activity decreased, and proMMP-2 activity increased., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils., Methods: Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls) or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels) were evaluated. Myocardial samples were collected for pathobiological evaluation., Results: Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α], intercellular (ICAM1) and vascular adhesion molecules (VCAM1) increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6), was downregulated. Myocardial expressions of sarco(endo)plasmic calcium-ATPase (SERCA2) and voltage-dependent calcium channel (Cacna1c) decreased, while protein kinase A (PKA) and calcium-calmodulin-dependent protein kinase (CaMK2D) expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1) did not change., Conclusions: We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.

Context. Brassica rapa is considered as natural source of antioxidants and is used to treat diabetes. Objective. Our study carried the impact of glucotoxicity induced in vivo and in vitro in vascular smooth muscle cells (VSMCs) in Psammomys and the therapeutic effect of Brassica rapa (AEBr). Materials and Methods. We administered a hyperglucidic diet (30% sucrose) for 9 months and a treatment for 20 days with AEBr at 100 mg/kg. VSMCs were submitted to D-Glucose (0.6%) for 48 hours and treated with AEBr (2100 μg/mL) for 24 hours. We measured, in blood metabolic parameters, the redox statues and inflammatory markers in adipose tissue. Histological study was effectuated in liver. In VSMCs, we measured markers of glucotoxicity (IRS1p Serine, AKT) inflammation (NO, MCP1, TNFα, and NF-κB) and oxidative stress (oxidants and antioxydants markers). Cell viability and apoptosis were estimated by the morphological study. Results. AEBr corrects the metabolic parameters and inflammatory and oxidative markers in blood and homogenate tissue and reduces lipid droplets in liver. It induces, in VSMCs, a significant decrease of IRS1p serine, cyt c, NO, MCP1, TNFα, NF-κB, protein, and lipid oxidation and increases cell viability, AKT, ERK1/2, catalase, and SOD activity. Conclusion. Brassica enhanced the antidiabetic, anti-inflammatory, and antioxidant defense leading to the protection of cardiovascular diseases.

Objective of the Study: The aim of our investigation was the study of the pathophysiology of the carotid artery in cases of nutritional stress in male atheroresistant Wistar rats., Materials and Methods: Were administered daily by gavage to experimental rats a high fat diet consisting of peanut oil, cholesterol (3%) and sodium cholate (1%). Throughout this experiment, we conducted monitoring of some biochemical parameters and the morpho-histopathology of the carotid cerebral artery. The results obtained are compared to those of control rats in the same experimental conditions., Results: We found that this fat diet resulted in experimental rats disruption of biochemical tests and tissular and cellular alterations in carotid wall. Indeed, the biochemical examination shows a significant increase of the parameters studied. Morphological examination revealed thickening of the carotid wall and histopathological examination of this artery, highlights the installation of a vascular remodeling from thickening of the intima-media to the installation of a probable atherosclerosis accompanied by a possible hyalinization and a net fibrosis., Conclusion: At the end of this study, although notes that our fat diet could cause a metabolic disorder that can cause multiple tissue and cell damage observed in cerebral artery "carotid" of atheroresistant rats., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: Lipogenesis is expressed in vascular smooth muscle cells (VSMCs), and such in situ lipogenesis could be providing the fatty acids for triglyceride synthesis and cholesterol esterification, and contributing to lipid accumulation in the arterial wall. This study investigated both the expression and regulation of lipogenesis in VSMCs to determine if they are modified in Psammomys obesus gerbils fed a high-fat diet as a model of insulin resistance and diabetes., Methods: Aortas were collected from diabetic and non-diabetic P. obesus for histological examination, measurement of lipogenic gene expression and VSMC culture., Results: The aortas of diabetic animals exhibited lipid deposits and foam cells as well as disorganization of elastic fibres. However, lipogenic gene expression was not modified. VSMCs in vitro from the aortas of diabetic animals had, compared with cells from non-diabetic animals, lower mRNA levels of SREBP-1c and ChREBP. An adipogenic medium stimulated moderate FAS and ACC1 expression in cells from both diabetic and non-diabetic animals, but glucose and insulin on their own had no such stimulatory action. Also, triiodothyronine (T3) had a clear stimulatory action, while angiotensin II had a moderate effect, in cells from non-diabetic P. obesus, but not from diabetic animals, whereas LXR agonists stimulated lipogenesis in cells from both animal groups., Conclusion: Lipogenesis is expressed in the arterial walls and VSMCs of P. obesus. However, its expression was not increased in diabetes, and did not respond to either T3 or angiotensin II. Therefore, lipogenesis in situ is unlikely to contribute to the accumulation of lipids in the arterial walls of diabetic P. obesus gerbils., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Background: Vascular smooth muscular cells (VSMC) express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma., Methods: We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma., Results: Zucker obese (ZO) and diabetic (ZDF) rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy) of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM., Conclusion: Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.

To simulate diabetic conditions, the effects of high glucose concentration on collagen synthesis and cholesterol level in cultured aortic smooth muscle cells of Psammomys were investigated. For collagen biosynthesis, smooth muscle cells (SMCs) were incubated in synthetic proliferative phase and in postconfluent phase with 3H-proline. Cellular cholesterol was determined by enzymatic method. Under high glucose concentration, the results showed morphological modifications characterized by morphometric cellular, nuclear, and nucleolar changes. In biochemical studies, the authors observed an increase of free and esterified cellular cholesterol as well as of total proteins, collagen biosynthesis, and alpha1 (I+III) and alpha2 (I) chains of collagen contained in the SMCs and in the extracellular matrix. These results showed the sensitivity of Psammomys aortic SMCs to high glucose concentration and would constitute an interesting cellular model to study atherosclerosis pathogeny in experimental diabetes.