The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Reciprocal crosslink among MeCP2/BDNF /CREB signaling pinpointed in autism spectrum disorder.

Autism spectrum disorder, or individual disability (ID), is a condition characterized by complications in social interaction, restricted repetitive behavior, and difficulties in social communication. Neuquinon (NQ) possess a powerful therapeutic potential in various neurodegenerative disease. Nevertheless, contributing to NQ's low water solubility and bioavailability, its medicinal use has been constrained. Liposomes were supposed to be prospective drug-delivering agents for NQ, crossing the blood-brain barrier (BBB), and reaching the target organs. The current investigation aims to track the signaling pathways that govern NQ and liposomal neuquinon (LNQ) action in autistic models generated by ethyl formic acid. The neurotransmitters gamma amino-butyric acid (GABA), acetylcholine (ACh), and acetylcholinesterase (AChE) in addition to, the gene expressions of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and methyl-CpG-binding protein 2 (MeCP2) and the DNA damage COMET analysis at different time intervals of the study, were assessed. EFA in a dose of 500 mg/kg BW was used to induce autism in rats, and then NQ and LNQ were administered in 10 mg/kg and 2 mg/kg BW, respectively. The results revealed that NQ and LNQ significantly down-regulated BDNF, GABA, and AChE; on the other hand, they up-regulated MeCP2, CREB gene expressions, and ACh action. NQ and LNQ displayed improvement in DNA damage in almost all brain regions after EFA alterations; even better results were noticed post-LNQ therapy. Therefore, it may be concluded that neuquinon and liposomal-loaded neuquinon have a therapeutic index versus EFA-induced autism in a rat model.

Synthesis, In Vitro Evaluation and Molecular Docking Studies of Novel Thiophenyl Thiazolyl-Pyridine Hybrids as Potential Anticancer Agents.

Many literature reports revealed the anticancer activity of pyridine and thiazole derivatives, especially in lung cancer. Therefore, a new series of thiazolyl pyridines linked with thiophene moiety via hydrazone group was prepared by one-pot multi-component reaction of (E)-1-(4-methyl-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl)thiazol-5-yl)ethanone with benzaldehyde derivatives and malononitrile in a good yield. Then, compound 5 and the thiazolyl pyridines were investigated for their in vitro anticancer activity against lung cancer (A549) cell line using MTT assay compared to doxorubicin as a reference drug. The structure of all the newly synthesized compounds was established based on spectroscopic data and elemental analyses. For better insight to investigate their mechanism of action on A549 cell line, docking studies were performed, targeting epidermal growth factor receptor (EGFR) tyrosine kinase. The results obtained revealed that the tested compounds displayed excellent anticancer activities against lung cancer cell line except 8c and 8f compared to reference drug. Based on the data obtained, it can be inferred that the novel compounds, as well as their key intermediate, compound 5, demonstrated potent anticancer activity against lung carcinoma by inhibiting EGFR.

Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model.

Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion: The administration of anti-inflammatory and antioxidant agents such as Co-Q10 and L Co-Q10 may represent a promising strategy to counteract pathological behaviors in ASD model via targeting organs, increasing retention time, and reducing side effects.

Eco-physiological response and genotoxicity induced by crude petroleum oil in the potential phytoremediator Vinca rosea L.

BACKGROUND: Phytoremediation is determined as an emerging green technology suitable for the safe remediation and restoration of polluted terrestrial and aquatic environments. In this study, the assessment of an ornamental plant, Vinca rosea L., as a phytoremediator of crude oil in polluted soils was conducted. In an open greenhouse experiment, plants were raised in sandy-clayey soils treated with 1, 3, 5, and 7% oil by weight. The experiment was conducted over 5 months. RESULTS: Total petroleum hydrocarbon (TPH) degradation percentage by V. rosea after a 5-month growth period ranged from 86.83 ± 0.44% to 59.05% ± 0.45% in soil treated with 1 and 7%, respectively. Plants raised in polluted soils demonstrated a dramatic reduction in germination rates, in addition to growth inhibition outcomes shown from decreased plant height. An increase in branching was observed with an increase in oil pollution percentages. Moreover, the phytomass allocated to the leaves was higher, while the phytomass witnessed lower values for fine roots, flowering and fruiting when compared to the controls. Apart from the apparent morphological changes, there was a decrease in chlorophyll a/b ratio, which was inversely proportional to the oil pollution level. The contents of carotenoids, tannins, phenolics, flavonoids, and antioxidant capacity were elevated directly with an increase in oil pollution level. The start codon-targeted (SCoT) polymorphisms and inter-simple sequence repeat (ISSR) primers showed the molecular variations between the control and plants raised in polluted soils. The genetic similarity and genomic DNA stability were negatively affected by increased levels of crude oil pollution. CONCLUSIONS: The ability of V. rosea to degrade TPH and balance the increased or decreased plant functional traits at the macro and micro levels of plant structure in response to crude oil pollution supports the use of the species for phytoremediation of crude oil-polluted sites. The genotoxic effects of crude oil on V. rosea still require further investigation. Further studies are required to demonstrate the mechanism of phenolic, flavonoid, and antioxidant compounds in the protection of plants against crude oil pollution stress. Testing different molecular markers and studying the differentially expressed genes will help understand the behavior of genetic polymorphism and stress-resistant genes in response to crude oil pollution.

Evaluation of the Anticancer Potential of Crude, Irradiated Cerastes cerastes Snake Venom and Propolis Ethanolic Extract & Related Biological Alterations.

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.

Synthesis and characterization of amoxicillin-loaded polymeric nanocapsules as a drug delivery system targeting Helicobacter pylori.

BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) is well known as the main cause of gastritis, gastroduodenal ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Approximately 50% of the world's population is infected with H. pylori. In Egypt, a high prevalence of H. pylori infections has been reported in the general population. This study aimed to prepare amoxicillin-loaded poly (ɛ-caprolactone) nanocapsules to increase its gastric stability and therapeutic activity of the molecule against H. pylori. MATERIALS AND METHODS: In this study, we used the water-oil-water double-emulsion technique to prepare spherical-shaped polymeric nanocapsules containing amoxicillin trihydrate as the core substance and biodegradable biocompatible poly (ɛ-caprolactone) as the shell material. RESULTS: The encapsulation efficiency obtained was 97.2% ± 0.8%. The hydrodynamic diameter of the prepared nanocapsules was 287 ± 8 nm with a positive zeta potential. In vitro release studies indicated that the polymeric nanocapsules showed decreased release percentages at pH 1.2, simulating the gastric fluid while relatively increased release at pH 7.0 where the H. pylori reside. The in vitro antibacterial assay showed better efficiency for amoxicillin nanocapsules than for the uncapsulated free amoxicillin, no efficiency was detected for the PCL nanocapsules indicated that the antibacterial due to amoxicillin alone. Cytotoxicity studies demonstrated less cytotoxicity for the polymeric nanocapsules in comparison with amoxicillin. CONCLUSIONS: In conclusion, we have demonstrated that biodegradable polymeric nanocapsules are useful drug delivery agents for increasing the gastric stability and therapeutic activity of amoxicillin trihydrate against H. pylori.

Anticancer Effect of Amygdalin (Vitamin B-17) on Hepatocellular Carcinoma Cell Line (HepG2) in the Presence and Absence of Zinc.

BACKGROUND: Amygdalin (Vitamin B-17) is a naturally occurring vitamin found in the seeds of the fruits of Prunus Rosacea family including apricot, bitter almond, cherry, and peach. OBJECTIVE: The purpose of this study was to examine the effect of amygdalin with and without zinc on hepatocellular carcinoma (HepG2) cell line. METHODS: MTT assay was used to evaluate the cytotoxicity of amygdalin without zinc, amygdalin + 20µmol zinc, and amygdalin + 800µmol zinc on HepG2 cell lines. The cell cycle distribution assay was determined by flow cytometry. Apoptosis was confirmed by Annexin V-FITC/PI staining assay. Moreover, the pathway of apoptosis was determined by the percentage of change in the mean levels of P53, Bcl2, Bax, cytochrome c, and caspase-3. RESULTS: Amygdalin without zinc showed strong anti-HepG2 activity. Furthermore, HepG2 cell lines treatment with amygdalin + 20µmol zinc and amygdalin + 800µmol zinc showed a highly significant apoptotic effect than the effect of amygdalin without zinc. Amygdalin treatment induced cell cycle arrest at G2/M and increased the levels of P53, Bax, cytochrome c, and caspase-3 significantly, while it decreased the level of anti-apoptotic Bcl2. CONCLUSION: Amygdalin is a natural anti-cancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in HepG2 treatment increased significantly by the addition of zinc.

Circulating miR-34a and miR-125b as Promising non Invasive Biomarkers in Egyptian Locally Advanced Breast Cancer Patients.

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level. Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology: Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%. miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV 41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value =0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2. Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic resistance associated with higher expression levels in non-responsive patients.

Propolis relieves the cardiotoxicity of chlorpyrifos in diabetic rats via alleviations of paraoxonase-1 and xanthine oxidase genes expression.

Pesticides cardiotoxicity in case of diabetic-induced cardiac complications is unidentified. The probable amelioration role of propolis is gauged against the cardiotoxic effects of chlorpyrifos in the diabetic rats through paraoxonase-1 (PON1) and xanthine oxidase (XO) genes dysregulation. Fifty-six male rats were distributed (n = 7) into eight groups. The first one saved as control whereas the 2nd, 3rd, and 4th were kept for propolis aqueous extract (100 mg/kg), diabetes (60 mg/kg streptozotocin) and chlorpyrifos (2.5 mg/kg), respectively. The 5th was diabetes/chlorpyrifos combination, while 6th, 7th, and 8th were intubated with propolis for four weeks after diabetic induction, chlorpyrifos intoxication, and their combination, respectively. The plasma glucose, lipid profiles, cardiac enzymes and interleukin-6 (IL-6) significantly elevated, while insulin decreased in the diabetic and combination groups. Although the cardiac acetylcholinesterase, total thiols, and PON1 significantly reduced after diabetic and/or chlorpyrifos gavage, the protein carbonyl, superoxide dismutase, catalase, and XO significantly elevated. The mRNA genes expression of PON1 and XO have also confirmed the enzymatic activities. Interestingly, propolis significantly restored the hyperglycemia, hypoinsulinemia, hyperlipidemia, IL-6 elevations, and antioxidant defense system disorder. These records revealed that the immunomodulatory, anti-diabetic and antioxidant tasks are fine pointers for the cardiovascular defender of propolis especially during diabetes and/or pesticides exposure.

Chemotherapeutic Resistance in Egyptian Acute Myeloid Leukemia Patients.

Background: Acute Myeloid Leukemia (AML) is a heterogeneous disorder with variable genetic abnormalities and cytogenetic alterations which provide a significant disease prognosis and determine response to therapy. Purpose: We aim to investigate the expression of the MDR1 gene in 100 Egyptian AML patients, to identify their role on both the progression and chemotherapeutic refractoriness together with assessment of known prognostic molecular markers; FLT3-ITD and NPM1 mutations. Methodology: Quantitative assessment of MDR1 gene expression was performed by quantitative RT-PCR. Additional prognostic molecular markers were determined as internal tandem duplications of the FLT 3 gene and nucleophosmin gene mutation A. Results: MDR1 gene expression levels and FLT3/ITD mutations were significantly higher in AML patients with resistant disease with P value <0.001 and 0.002 respectively. However, NPM1 was insignificantly higher in patients with CR P-value 0.14. In MDR positive group, wild FLT3/ITD with or without NPM1 mutation was favorable in achieving CR with p value 0.02. MDR negative group, wild FLT3/ITD with or without NPM1 mutation showed insignificantly higher CR rates with p value (0.35). Kaplan-Meier curves revealed statistically significant difference between MDR1-negative and MDR1-positive patients regarding their DFS and OS between the two groups where DFS and OS were higher in MDR1-negative patients with p value 0.004 and 0.01, respectively. Conclusion: The results obtained by the current work together with the previous researches concerning the study of multidrug resistance genes in AML patients provide additional evidence of the role played by these genes as predictors of chemoresistance and poor treatment outcome.

Garlic and allopurinol attenuate hepatic apoptosis induced by fipronil in male albino rats.

Fipronil (FPN) can induce oxidative tissue damage and may be contemplated as an apoptosis inducer. Our aim is to investigate the possible hepatoprotective roles of garlic or allopurinol (ALP) against fipronil subacute toxicity. Thirty-six mature male albino rats were randomly divided into six groups; the first group was saved as control (C), the 2nd (G) was orally intubated with 500 mg/kg aqueous garlic extract, and the 3rd (A) received 150 mg/L allopurinol in their drinking water. The 4th group (F) was administered 13.277 mg/kg fipronil by gavage, while the 5th (G + F) and 6th (A + F) groups received the same doses of garlic and allopurinol, respectively two hours before fipronil intoxication. Our results revealed that FPN significantly increased the hepatic malondialdehyde, protein carbonyl levels, and the enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase, but it decreased glutathione-S-transferase compared to the control group. Moreover, FPN exhibited significant up-regulation in the hepatic pro-apoptotic (Bax) and caspase-3 genes expression, down-regulation in the anti-apoptotic (Bcl-2) mRNA gene expression and induced DNA fragmentation. Surprisingly, garlic or allopurinol co-treatment ameliorated the hepatic lipid peroxidation, antioxidants disruption, and apoptosis induced by FPN. In conclusion, garlic and allopurinol relieved the oxidative injury and reduced the fipronil-induced apoptosis probably by improving the tissue antioxidant defense system.

Nephroprotective effect of green tea, rosmarinic acid and rosemary on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute renal toxicity in Wistar rats.

The present study was designed to investigate the chemoprotective effect of green tea extract (GTE), rosmarinic acid (RA) and rosemary extract (RE) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted nephrotoxicity in rats. Forty male rats were categorized into five: Group I included healthy rats, group II received DEN+Fe-NTA, group III received 200 mg/kg b.wt. of RE+DEN+Fe-NTA, group IV received 1 g/kg b.wt. of GTE+DEN+Fe-NTA and group V received 50 mg/kg b.wt. of RA+DEN+Fe-NTA. RE, GTE, RA were given orally for 14 days before single intraperitoneal administration of DEN (160 mg/kg) till the end of the experiment. Eighteen days after DEN, a single intraperitoneal dose of Fe-NTA (5 mg Fe/kg) was administrated to rats to promote nephrotoxicity. The biochemical parameters were analyzed in serum at time intervals while the malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were assessed in both serum and renal tissues. Kidney from each group was histopathologically examined at time intervals. The administration of Fe-NTA after DEN dose to albino rats resulted in acute nephrotoxicity which was characterized by a highly significant elevation of serum urea, creatinine, uric acid (p=0.000), serum and renal MDA and TNF-α (p=0.000) with vacuolation of epithelial lining renal tubules. The administration of RE, GTE and RA prior to DEN+Fe-NTA treatment significantly ameliorated the observed increased levels of the above mentioned parameters. GTE, RA & RE exerted a protective effect against renal toxicity with GTE showing a more pronounced effect on renal function parameters while RA showed the best antioxidant impact.

Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. METHODS: Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. RESULTS: The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. CONCLUSION: Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin.

Hepatoprotective effects of parsley, basil, and chicory aqueous extracts against dexamethasone-induced in experimental rats.

AIM: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. MATERIALS AND METHODS: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. RESULTS: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. CONCLUSIONS: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Circulating levels and clinical implications of epithelial membrane antigen and cytokeratin-1 in women with breast cancer: can their ratio improve the results?

Immunohistochemical studies proved that the presence of breast cancer (BrCa) is accompanied by elevated levels of epithelial membrane antigen (EMA) and decreased levels of cytokeratin-1 (CK1). We, therefore, hypothesize that the serum EMA/CK1 ratio may serve as a promising biomarker for early diagnosis of breast cancer. The circulating levels of EMA and CK1 were determined by Western blot and enzyme-linked immunosorbent assay (ELISA) in sera from 102 women with BrCa and 90 women as controls (40 with benign breast disease and 50 healthy). EMA at 130 kDa and CK1 at 67 kDa were identified, purified, and quantified in sera of BrCa patients using ELISA. EMA/CK1 ratio values were found to discriminate BrCa patients from controls (P < 0.0001) with high diagnostic ability (area under the curve [AUC] = 0.901, sensitivity = 82, specificity = 76). The sensitivity and specificity for early-stage (≤ T2) BrCa were 72 and 76%, respectively. The ratio values of patients with late-stage (>T2) tumors were significantly higher than those of patients with early-stage (≤ T2) tumors. Moreover, higher grades (grades 2-3) were associated with higher values than grade 1 tumors. AUC values in different BrCa patients who had early stage, low grade, or size ≤ 2 cm were 0.855, 0.762, and 0.839, respectively. AUC values of patients with positive lymph node or positive distant metastasis were 0.907 and 0.913, respectively. We show for the first time the impact of serum EMA and CK1 ratio in BrCa detection. Differential EMA/CK1 values may serve as a diagnostic marker in early-stage breast cancer patients.

Implication of protein kinase R gene quantification in hepatitis C virus genotype 4 induced hepatocarcinogenesis.

BACKGROUND: Protein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question. METHODS: We report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed. RESULTS: If PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene. CONCLUSION: The findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.