Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Egypt. There is still a risk for HCC development even after eradicating hepatitis C virus (HCV) by direct-acting antivirals (DAAs). Chitinase-3-like-protein-1 (CHI3L1), a biomarker for predicting many diseases, plays an essential role in inflammation, angiogenesis, and antiapoptosis. Tolloid-like protein 1 (TLL1) may be involved in hepatic fibrogenesis and carcinogenesis. This study aimed to determine the role and combined effect of CHI3L1 (rs880633), TLL1 (rs1503298), and an intergenic (rs597533) polymorphisms on the risk of developing HCC in Egyptian patients after achieving sustained virological response (SVR) by DAAs. Blood samples were collected from 68 HCC patients, 77 non-HCC subjects, and 80 healthy controls. The DNA was extracted and analyzed for rs880633, rs1503298, and rs597533 using Genotyping TaqMan™ assay. The result of the present study showed a significant difference in genotypes and alleles frequencies in both (rs880633) and (rs597533) in HCC group as compared to healthy control and also as compared to the non-HCC group. However, regarding to (rs1503298) genotypes and alleles between the HCC and non-HCC groups, there were no significant differences. Combined polymorphism in more than one gene simultaneously showed a higher risk to HCC after SVR than an individual locus. Both allelic and genotypic variations of the CHI3L1 gene (rs880633) and an intergenic (rs597533) seemed to be significant predictors confirming a great risk for HCC susceptibility in Egyptian patients achieved SVR. Patients with a polymorphism in more than one gene showed an increased risk to HCC after SVR rather than individual locus.

Utility of novel 2-furanones in synthesis of other heterocyclic compounds having anti-inflammatory activity with dual COX2/LOX inhibition.

Inflammation is associated with the development of several diseases comprising cancer and cardiovascular disease. Agents that suppress cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, besides chemokines have been suggested to minimise inflammation. Here, a variety of novel heterocyclic and non-heterocyclic compounds were prepared from novel three furanone derivatives. The structures of all synthesised compounds were confirmed by elemental and spectral analysis including mass, IR, and 1H-NMR spectroscopy. Anti-inflammatory activities of these synthesised compounds were examined in vitro against COX enzymes, 15-LOX, and tumour necrosis factor-α (TNF-α), using inhibition screening assays. The majority of these derivatives showed significant to high activities, with three pyridazinone derivatives (5b, 8b, and 8c) being the most promising anti-inflammatory agents with dual COX-2/15-LOX inhibition activities along with high TNF-α inhibition activity.

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.

Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal chemistry. Herein, we report the design, synthesis molecular modelling and biological evaluation of novel hybrids containing pyrazole, naphthalene and pyrazoline/isoxazoline moiety. Chalcones 2a-e were synthesized efficiently and were used as starting materials for synthesis of a variety of heterocycles. A novel series of pyrazoline 3a-e, phenylpyrazoline 4a-e, isoxazoline 5a-e and pyrazoline carbothioamide derivatives 6a-e were synthesized and screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide radical scavenging assay as well as 15-lipoxygenase (15-LOX) inhibition activity. Compounds 3a, 4e, 5b, 5c, 6a, 6c, and 6e showed excellent radical scavenging activity in all three methods in comparison with ascorbic acid and 15-LOX inhibition potency using quercetin as standard then were subjected to in vivo study. Catalase (CAT) activity, glutathione (GSH) and malondialdehyde (MDA) levels were assayed in liver of treated rats. Compounds 5b, 5c, and 6e showed significant in vivo antioxidant potentials compared to control group at dose of 100 mg/kg B.W. Molecular docking of compound 6a endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.

Inflammasome Genes' Polymorphisms in Egyptian Chronic Hepatitis C Patients: Influence on Vulnerability to Infection and Response to Treatment.

Chronic inflammation is a pivotal contributor to the liver damage mediated by hepatitis C virus (HCV). The NOD-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome is activated by HCV in both hepatocytes and Kupffer cells. The aim of our study was to investigate the association of nine single-nucleotide polymorphisms in four inflammasome genes (NLRP3, CARD8, IL-1ß, and IL-18) with the susceptibility to HCV infection and outcome of interferon treatment in 201 Egyptian chronic hepatitis C patients and 95 healthy controls. The genotyping was conducted using TaqMan predesigned SNP assay. In the comparative analysis, the CC genotype of the NLRP3 rs1539019 was found to be associated with the lower risk to chronic HCV infection (OR: 0.33, 95% CI: 0.17-0.62). This association was also found for the CA genotype and the A allele of the NLRP3 rs35829419 (OR: 0.18 and 0.22, respectively), in addition to the GG genotype and G allele of IL-18 rs1946518 (OR: 0.55 and 0.61, respectively). In contrast, the AA genotype of the IL-1ß rs1143629 was significantly more frequent in HCV patients (OR: 1.7, 95% CI: 1-2.86). Notably, the frequency of the AA genotype of NLRP3 rs1539019 was significantly higher in patients with lack of response (NR) to the interferon treatment (OR: 1.95, 95% CI: 1-3.7). A similar association was found for both the CC genotype and C allele of the NLRP3 rs35829419 (OR: 2.78 and 2.73, respectively) and for the TT genotype and T allele of CARD8 rs2043211 (OR: 2.64 and 1.54, respectively). Yet, the IL-1ß (rs1143629, rs1143634) and IL-18 (rs187238, rs1946518) polymorphisms did not show any significant association with response to interferon treatment. In conclusion, this study reports, for the first time, the association of genetic variations in NLRP3 with hepatitis C susceptibility and response to treatment in Egyptian patients. However, further large-scale studies are recommended to confirm our findings.

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Thiouracil Derivatives as Potential Antithyroid Agents.

Hyperthyroidism is the result of uncontrolled overproduction of the thyroid hormones. One of the mostly used antithyroid agents is 6-n-propyl-2-thiouracil (PTU). The previously solved X-ray crystal structure of the PTU bound to mammalian lactoperoxidase (LPO) reveals that the LPO-PTU binding site is basically a hydrophobic channel. There are two hydrophobic side chains directed towards the oxygen atom in the C-4 position of the thiouracil ring. In the current study, the structural activity relationship (SAR) was performed on the thiouracil nucleus of PTU to target these hydrophobic side chains and gain more favorable interactions and, in return, more antithyroid activity. Most of the designed compounds show superiority over PTU in reducing the mean serum T4 levels of hyperthyroid rats by 3% to 60%. In addition, the effect of these compounds on the levels of serum T3 was found to be comparable to the effect of PTU treatment. The designed compounds in this study showed a promising activity profile in reducing levels of thyroid hormones and follow up experiments will be needed to confirm the use of the designed compounds as new potential antithyroid agents.

Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients.

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

CONTEXT: In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. OBJECTIVE: The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. MATERIAL AND METHODS: The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. RESULTS: Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. DISCUSSION AND CONCLUSION: The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2.

Sorafenib is a potent inducer of ferroptosis used to manage hepatocellular carcinoma (HCC). The ferroptosis induced by sorafenib activates the p62-Keap1-Nrf2 pathway. Abnormal activation of Nrf2 reduces sorafenib's efficiency and ferroptosis action and induces sorafenib's resistance. Consequently, our study tried to study the effect of a novel combination of sorafenib and Camptothecin (CPT, Nrf2 inhibitor) to improve sorafenib's ferroptosis action and reduce sorafenib resistance in the treatment of HCC. We evaluated the efficacy of sorafenib and/or CPT using HepG2 and Huh7 cell lines. MTT assay evaluated the anti-proliferation effects. The combination index (CI) and dose reduction index (DRI) were calculated using Isobologram analysis. Malondialdehyde (MDA), total antioxidant capacity (TAC), iron concentration, glutathione peroxidase (GPX4), and glutathione reductase (GR) activity assays were used to determine the ferroptosis action of drugs. Western blot was used to investigate the expression of the implicated proteins. Bioinformatics tools were used to determine the correlation between these proteins. Finally, the HPLC technique is used to measure cellular drug uptake. Our results revealed a strong synergism between sorafenib and CPT. The synergetic combination significantly increases lipid peroxidation and iron concentration, decreases TAC, GPX4 and GR activity, and reduces the expression of both Nrf2 and SLC7A11. The downregulation of Nrf2 expression has a vital role in the reduction of resistance mediators to sorafenib against HCC cells like (p62, MT1G, and ABCG2) and improves the cellular uptake of sorafenib. The current study provided evidence that Nrf2 inhibition by CPT improves sorafenib's sensitivity and reduces sorafenib's resistance via the augmentation of sorafenib's ferroptosis action.

Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population.

Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001). Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.

Melaleuca rugulosa (Link) Craven Tannins: Appraisal of anti-inflammatory, radical scavenging activities, and molecular modeling studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities. AIM OF THE STUDY: Our study aimed to investigate the metabolic profile of the M. rugulosa polyphenol-rich fraction along with determination of its anti-inflammatory potential, free radical scavenging and antiaging activities supported with virtual understanding of the mode of action using molecular modeling strategy. MATERIALS AND METHODS: The anti-inflammatory activity of the phenolic rich fraction was investigated through measuring its inhibitory activity against inflammatory mediators viz tumor necrosing factor receptor-2 (TNF-α) and cyclooxygenases 1/2 (COX-1/2) in a cell free and cell-based assays. Moreover, the radical scavenging activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene assays, while the antiaging activity in anti-elastase, anti-collagenase, and anti-tyrosinase inhibitory assays. Finally, the biological findings were supported with molecular docking study using MOE software. RESULTS: The chromatographic purification of the polyphenol-rich fraction of Melaleuca rugulosa (Link) Craven afforded fourteen phytoconstituents (1-14). The anti-inflammatory gauging experiments demonstrated inhibition of inflammatory-linked enzymes COX-1/2 and the TNF-α at low µg/mL levels in the enzyme-based assays. Further investigation of the underlying mechanism was inferred from the quantification of protein levels and gene expression in the lipopolysaccharide (LPS)-activated murine macrophages (RAW264.7) in vitro model. The results revealed the reduction of protein synthesis of COX-1/2 and TNF-α with the down regulation of gene expression. The cell free in vitro radical scavenging assessment of the polyphenol-rich fraction revealed a significant DPPH reduction, peroxyl radicals scavenging, and ß-carotene peroxidation inhibition. Besides, the polyphenol-rich fraction showed a considerable inhibition of the skin aging-related enzymes as elastase, collagenase, and tyrosinase. Ultimately, the computational molecular modelling studies uncovered the potential binding poses and relevant molecular interactions of the identified polyphenols with their targeted enzymes. Particularly, terflavin C (8) which showed a favorable binding pose at the elastase binding pocket, while rosmarinic acid (14) demonstrated the best binding pose at the COX-2 catalytic domain. In short, natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions. CONCLUSION: Natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions.

New phenolic compounds from Calothamnus quadrifidus R.Br. aerial parts and their antioxidant activity.

Two new compounds calothphenone (1) and 6-methoxy kaempferol 3-O-(6″-E-p-coumaroyl)-ß-d-glucopyranoside (6-methoxy tiliroside) (2) along with six known compounds viz gallic acid (3), methyl gallate (4), kaempferol 3-O-(6″-E-p-coumaroyl)-ß-d-glucopyranoside (tiliroside) (5), castalagin (6), kaempferol (7) and quercetin (8) were isolated from the ethyl acetate fraction (EAF) of 80% aqueous methanol extract of Calothamnus quadrifidus aerial parts. Their structure was established based on different chemical and spectroscopic techniques (1H-/13C-NMR and 2D NMR). Antioxidant activity for EAF and compounds 1, 2 and 5 was evaluated using DPPH, superoxide radical and nitric oxide (NO) inhibition methods. EAF exhibited strong activity to inhibit DPPH, superoxide and NO radicals. Moreover, all tested compounds demonstrated a close high ability to inhibit superoxide and NO radicals in comparison to ascorbic acid, but they exerted lower activity towards DPPH radical.[Figure: see text].

Targeting NUPR1 for Cancer Treatment: A Risky Endeavor.

NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 regulates a complex network of pathways that may be affected by its silencing, which can cause varying effects. Its role in some types of cancer has been reported but remains incompletely understood, whereas its roles in other types of cancers have not been reported yet. Therefore, targeting NUPR1 for cancer treatment remains challenging and risky.

Effects of gamma-irradiation on antibiotic resistance and diagnostic molecular markers of methicillin-resistant Staphylococcus aureus in Egyptian cancer patients.

Purpose: This in-vitro study aimed to assess in 120 [40 community-acquired (CA-MRSA) & 80 hospital-acquired (HA-MRSA)] isolates from cancer patients whether the transmissible staphylococcal cassette chromosome mec (SCCmec) typing, and the Panton-Valentine leukocidin (PVL) virulence genes detection could be employed as tools for molecular diagnostic purposes to distinguish both methicillin-resistant Staphylococcus aureus (MRSA) categories in radiotherapy treated cancer patients.Materials and methods: SCCmec typing was determined by the combination of the type of the cassette chromosome recombinase genes (ccr) gene complex and the class of the methicillin resistance (mec) gene complex. Besides, a rapid slide latex agglutination test (LAT) and antibiotic resistance spectrum determination before and after irradiation were performed.Results: In the strict sense, with the effect of irradiation; the presence of SCCmec subtypes IVa (22.5% vs. 10.0%), b (47.5% vs. 25.0%), & d (7.5 vs. 2.5%) or type V (15.0% vs. 7.5%) genetic elements and PVL genes (p < .001) were not proved as a signature for CA-MRSA. While, the larger SCCmec types II, and III elements were not detected in 14, and 19 from the 38, and 36 typed HA-MRSA isolates (p < .001), respectively. Remarkable effects on class A & class B mec gene complex and type2, type 3 & type 5 ccr gene complex and an increase in agglutination reaction strength in response to gamma irradiation external stimulus were observed.Conclusions: Different heterogeneous genetic composition with upregulation mecA gene expression was detected after irradiation in the HA- MRSA studied population. CA-MRSA showed remarkable ability to acquire multi-antibiotic resistance after irradiation and propose a novel paradigm for future chemotherapy against the multi-resistant pathogens whose proliferation especially among immunocompromised cancer patients is on the increase.

The combined effect of IL-17F and CCL20 gene polymorphism in susceptibility to multiple sclerosis in Egypt.

BACKGROUND: Levels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the recruitment of T helper (Th17) cells to site of inflammation. OBJECTIVES: Determine the value of single nucleotide polymorphism of CCL20 (rs6749704) and IL-17F (rs763780) genes and their concomitant effect on the serum CCL20 level and susceptibility to MS in Egyptian patients. SUBJECTS AND METHODS: Blood samples were collected from 83 patients and 95 healthy subjects. Serum levels of CCL20 were measured by ELISA. The DNA was analyzed for rs6749704 and rs763780 using Genotyping Taqman assay. RESULTS: The mean serum levels of CCL20 in the MS group were significantly higher than healthy group (P < 0.001). Frequencies of CT genotype of rs6749704 in CCL20 gene and C allele in MS patients were significantly higher compared to controls. Also significant increase of rs763780 in IL-17F gene was detected in MS patients. Concomitant polymorphism in both genes in MS patients showed an increase risk to MS rather than individual locus. CONCLUSION: CCL20 may play an important role in the pathogenesis of MS. Both allelic variation of (rs6749704) within CCL20 gene and (rs763780) within IL-17F gene can be considered risk factor for development of MS in Egyptian patients.

Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test.

BACKGROUND: Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). OBJECTIVE: Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. DESIGN: Cross-sectional prospective. SETTING: Multiple non-tertiary care hospitals. PATIENTS AND METHODS: HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods. MAIN OUTCOME MEASURES: The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. SAMPLE SIZE: 520 subjects. RESULTS: Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). CONCLUSION: Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. LIMITATIONS: A second step TST was not feasible within 2-3 weeks. CONFLICT OF INTEREST: None.

Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes: A case-control study.

BACKGROUND: Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. However, the mechanism underlying the IR in chronic HCV is obscure. Hepatokines are group of liver-derived protein, which affect the glucose and lipid metabolism in several tissues. Fetuin A (also known as human α2-HS-glycoprotein) is one of the hepatokines, which was recognized as a natural inhibitor of the insulin receptor tyrosine kinase in liver and skeletal muscle. Additionally, selenoprotein P has emerged as an important hepatokine, which primarily acts as selenium transporter and has been reported to be implicated in glucose homeostasis in human. OBJECTIVE: The aim of the current case-control study was to investigate the serum levels of both fetuin A and selenoprotein P in chronic hepatitis C patients with or without T2DM and to correlate their levels with other biochemical parameters of insulin resistance. MAIN FINDINGS: Our results showed that, serum fetuin A levels increased significantly in HCV patients compared with controls (P<0.01) and surplus increase was found in HCV with concomitant T2DM (P>0.001). However, selenoprotein P levels significantly elevated only in patients with both HCV and T2DM (P<0.05) compared with the healthy subjects. Both fetuin A and selenoprotein P were positively correlated with fasting blood glucose. Yet, only fetuin A was significantly correlated to the HOMA-IR (r=0.28; P=0.03). CONCLUSIONS: These results indicate crucial roles played by fetuin A and selenoprotein P in the IR caused by HCV and that both hepatokines may be targets for the development of therapies to treat or inhibit insulin resistance associated to HCV. However, further studies on large scale should be conducted to confirm our findings.

CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM.

BACKGROUND: In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. METHODS: Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l ¼CTX«) were measured and compared to the results of 20 age-matched healthy controls. RESULTS: After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. CONCLUSIONS: Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sex-related reference.

The protective effect of Phoenix dactylifera L. seeds against CCl4-induced hepatotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Egyptian medicine, Phoenix dactylifera L. (date palm) seeds are listed in folk remedies for the management of diabetes, liver diseases and gastrointestinal disorders. The present study was conducted to investigate the protective effect of Phoenix dactylifera L. seeds aqueous suspension against the chemically-induced hepatic injury in rats. METHODS: Liver injury was achieved by exposing Wistar rats to CCl4 (10% in olive oil; 0.5 mL/rat; IP) twice a week for 4 weeks. Along with CCl4, aqueous suspensions of raw or roasted Phoenix dactylifera seeds (1.0 g/kg) were administered orally in a daily manner. RESULTS: Our results demonstrated that Phoenix dactylifera seeds significantly improved the CCl4-induced alterations in liver function parameters (AST, ALT, ALP and albumin). Moreover, the CCl4-induced oxidative stress, represented by elevated thiobarbituric acid reactive substance (TBARS), nitric oxide and oxidative DNA damage, was ameliorated by Phoenix dactylifera seeds treatment. In addition, Phoenix dactylifera seeds restored the activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione S-transferase) that were declined after CCl4 treatment. Examination of liver histopathology revealed that Phoenix dactylifera seeds attenuate the incidence of liver lesions (including vacuolization and fibroblast proliferation) triggered by CCl4 intoxication. CONCLUSION: The Phoenix dactylifera seeds could be a promising candidate for protection against the CCl4-induced liver intoxication, and this hepatoprotective effect might be attributed to the antioxidant and free radical scavenging activities.