Background: Free doxorubicin (Dox) is used as a chemotherapeutic agent against hepatocellular carcinoma (HCC), but it results in cardiotoxicty as a major side effect. Hence, a controlled Dox drug delivery system is extremely demanded. Methods: Dox was loaded into the non-toxic biodegradable polycaprolactone (PCL) nanocapsules using the double emulsion method. Characterization of Dox-PCL nanocapsules was done using transmission electron microscopy and dynamic light scattering. Encapsulation efficiency and drug loading capacity were quantified using UV–visible spectrophotometry. Drug release was investigated in vitro at both normal (7.4) and cancer (4.8) pHs. Cytotoxicity of Dox-PCL nanocapsules against free Dox was evaluated using the MTT test on normal (Vero) and hepatic cancer (HepG2) cell lines. Results: Spherical nanocapsules (212 ± 2 nm) were succeffully prepared with a zeta potential of (-22.3 ± 2 mv) and a polydisperse index of (0.019 ± 0.01) with a narrow size distribution pattern. The encapsulation efficiency was (73.15 ± 4%) with a drug loading capacity of (16.88 ± 2%). Importantlly, Dox-release from nanocapsules was faster at cancer pH (98%) than at physiological pH (26%). Moreover, although Dox-PCL nanocapsules were less toxic on the normal cell line (GI 50 = 17.99 ± 8.62 µg/ml) than free Dox (GI 50 = 16.53 ± 1.06 µg/ml), the encapsulated Dox showed higher toxic effect on cancer HepG2 cells compared to that caused by the free drug (GI 50 = 2.46 ± 0.49 and 4.22 ± 0.04 µg/ml, respectively). Conclusion: The constructed Dox-PCL nanocapsules constitute a potentially controlled anti-HCC therapy with minimal systemic exposure. Graphical

Background: Helicobactor pylori (H. pylori) virulence markers would be useful to predict peptic ulcer disease (PUD) or gastric cancer. Aim: In Egypt, since inadequate data are present regarding H. pylori virulence–related genes in different age group patients with gastro-duodenal diseases, it becomes crucial to study the clinical status of cagA, vacA and iceA1 genotypes of H. pylori strains recovered from patients with dyspepsia. Subjects and methods: The study included 113 dyspeptic patients who were exposed to upper gastrointestinal endoscopic examination. Four antral biopsies were obtained from each patient for the analysis of H. pylori infection by rapid urease test and detection of 16S rRNA. Results: Sixty (53.1%) patients were confirmed to be infected with H. pylori. Upon endoscopy, gastritis was revealed in 27 patients (45%) and10 patients (16.7%) had PUD. Of the 60 H. pylori strains, 39 (65%) had at least one virulence gene. Six different genotypic forms were recognized; vacA (9/60), iceA1 (1/60), vacA/cagA (7/60), vacA/iceA1 (13/60), vacA/cagA/iceA1 (8/60) only one of cagA/iceA type and we could not detect cagA. The overall vacA, iceA1and cagA genes identified were 61.6%, 38.8%, 26.6% respectively, by PCR-based molecular testing. The vacA gene status was highly significant related to gastritis patient (P ≤ 0.036). The vacA s1m1 and s2m2 alleles were significantly found in 50% of H. pylori infected patients with PUD and with gastritis 57.1% respectively (P ≤ 0.01). Conclusion: In conclusion, the main genotype combinations in the studied Egyptian patients were; vacAs2m2/iceA1, vacAs1m1/cagA, mostly associated with gastritis, and vacAs1/cagA/icA, mainly in PUD. The less virulent (s2, s2m2) H. pylori genotypes were found in patients aged over 43 years

Context: Linum usitatissimum (Linn); known as Flaxseed, is one of the most important medicinal plants traditionally used for health benefits and also as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents, and evaluation of the antioxidant, antiinflammatory and anticancer activities have been performed on hexane, ethyl acetate, n-butanol, and methanol extracts and also on fractions of methanol extract (hexane, ethyl acetate, and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts was tested on Hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7). Results: The methanolic extract and its ethyl acetate fraction showed higher contents of total phenols and flavonoids. Also, the methanolic extract showed a higher antioxidant activity. The butanolic and ethyl acetate fractions at concentration 500μg/ml yielded a higher percent of inhibition of protein denaturation; 87.9% and 90%, respectively. The ethyl acetate fraction and the methanolic extract showed an obvious anticancer activity against HepG2 and MCF7 (IC50=60±0.24 and 29.4±0.12μg. ml-1) and (IC50=94.7±0.21 and 227±0.48μg. ml-1), respectively. The GC-MS analysis showed that the methanolic extract had 32 compounds whereas the ethyl acetate and butanol fractions contained 40 and 36 compounds, respectively. Conclusion: Flaxseed contains different biologically active compounds that have been found to possess various activities, which can protect the human body against several diseases.

Background: Enterococci are intrinsically resistant to clinically achievable concentrations of aminoglycosides. However, high-level resistance to aminoglycosides (HLAR) is primarily due to the acquisition of genes encoding aminoglycoside-modifying enzymes (AMEs). Aminoglycosides along with cell wall inhibitors are given clinically for treating enterococcal infections. The current study was conducted to investigate the rate of HLAR and to determine aminoglycoside resistance encoding genes profile in enterococcal isolates from different clinical specimens. Results: From 120 Enterococcus species, 50 (41.7%) enterococcal isolates were proven to have HLAR, 78% (39/50) have high-level gentamicin resistance (HLGR), and 74% (37/50) were high-level streptomycin-resistant (HLSR). HLGR isolates carried aminoglycoside modifying gene aac (6′)-Ie-aph (2′)-Ia in 26/39 (66.7%) of isolates, whereas 32/37 (86.5%) of HLSR carried aph (3′)-IIIa gene and were observed in E. faecalis, E. faecium, E. gallinarum, and E. casseliflavus. The aph (2′)-Ib, aph (2′)-Ic, and aph (2′)-Id that encode HLGR could not be detected. Conclusions: The high detection rate of HLAR among the studied Enterococcus species and the coexistence of HLGR and HLSR strains provide crucial insights to the necessity of routine testing for HLAR in the microbiology lab. The main AME genes among HLGR and HLSR enterococci were aac (6′)-Ie-aph (2″)-Ia and aph (3′)-IIIa, respectively.

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(ε-caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 ± 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG–Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections.