Antibacterial, antibiofilm, and anticancer activity of silver-nanoparticles synthesized from the cell-filtrate of Streptomyces enissocaesilis.

Silver nanoparticles (Ag-NPs) have a unique mode of action as antibacterial agents in addition to their anticancer and antioxidant properties. In this study, microbial nanotechnology is employed to synthesize Ag-NPs using the cell filtrate of Streptomyces enissocaesilis BS1. The synthesized Ag-NPs are confirmed by ultraviolet-visible (UV-Vis), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Also, the effects of different factors on Ag-NPs synthesis were evaluated to set the optimum synthesis conditions. Also, the antibacterial, antibiofilm, and anticancer activity of Ag-NPs was assessed. The X-ray diffraction (XRD) analysis confirmed the crystalline nature of the sample and validated that the crystal structure under consideration is a face-centered cubic (FCC) pattern. The TEM examination displayed the spherical particles of the Ag-NPs and their average size, which is 32.2 nm. Fourier transform infrared spectroscopy (FTIR) revealed significant changes in functionality after silver nanoparticle dispersion, which could be attributed to the potency of the cell filtrate of Streptomyces enissocaesilis BS1 to act as both a reducing agent and a capping agent. The bioactivity tests showed that our synthesized Ag-NPs exhibited remarkable antibacterial activity against different pathogenic strains. Also, when the preformed biofilms of Pseudomonas aeruginosa ATCC 9027, Salmonella typhi ATCC 12023, Escherichia coli ATCC 8739, and Staphylococcus aureus ATCC 6598 were exposed to Ag NPs 50 mg/ml for 24 hours, the biofilm biomass was reduced by 10.7, 34.6, 34.75, and 39.08%, respectively. Furthermore, the Ag-NPs showed in vitro cancer-specific sensitivity against human breast cancer MCF-7 cell lines and colon cancer cell line Caco-2, and the IC50 was 0.160 mg/mL and 0.156 mg/mL, respectively. The results of this study prove the ease and efficiency of the synthesis of Ag-NPs using actinomycetes and demonstrate the significant potential of these Ag-NPs as anticancer and antibacterial agents.

Microbiological and molecular studies on a multidrug-resistant Pseudomonas aeruginosa from a liver transplant patient with urinary tract infection in Egypt.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants. METHODS: In this study, a number of 30 individuals who underwent liver transplants were registered. Ninety urine and 60 wound site swab samples were collected and processed for culturing, identification, and antimicrobial sensitivity. Extensively drug-resistant strain EMARA01 was confirmed through Sanger sequencing and was then processed for whole genome sequencing to characterize the genomic pattern. Sequencing data were processed for de novo assembly using various tools and databases, including genome annotation, serotype identification, virulence factor genes, and antimicrobial resistance gene. Pangenome analysis of randomly selected 147 reference strains and EMAR01 sequenced strain was performed using the Bacterial Pan Genome Analysis (BPGA) software. RESULTS: Of these total examined samples, nosocomial infection due to P. aeruginosa was detected in twelve patients' samples. AST analysis showed that P. aeruginosa strains exhibit resistance to tobramycin, erythromycin, and gentamicin, followed by piperacillin and ofloxacin, and no strains exhibit resistance to meropenem and imipenem. The CARD database identified 59 AMR genes similar to the EMAR01 strain genome and mostly belong to the family involved in the resistance-nodulation-cell division (RND) antibiotic efflux pump. Five genes; nalC, nalD, MexR, MexA, and MexB, exhibit resistance to 14 classes of antibiotics, while two AMR; CpxR, and OprM, exhibit resistance to 15 classes of drugs. Pangenome analysis revealed that the pan-genome remained open, suggesting the potential for acquiring accessory and unique genes. Notably, the genes predominantly involved in amino acid transport metabolism were identified using the KEGG database. CONCLUSIONS: This study provides valuable insights into the antimicrobial resistance profile, genetic features, and genomic evolution of P. aeruginosa strains causing UTIs in liver transplant patients. The findings emphasize the significance of comprehending AMR mechanisms and genetic diversity in P. aeruginosa for developing effective treatment strategies and infection control measures.

Natural Peroxides from Plants: Historical Discovery, Biosynthesis, and Biological Activities.

Naturally occurring peroxides received great interest and attention from scientific research groups worldwide due to their structural diversity, versatile biological activities, and pharmaceutical properties. In the present review, we describe the historical discovery of natural peroxides from plants systematically and update the researchers with recently explored ones justifying their structural caterogrization and biological/pharmaceutical properties intensively. Till the end of 2023, 192 peroxy natural products from plants were documented herein for the first time implying most categories of natural scaffolds (e.g. terpenes, polyketides, phenolics and alkaloids). Numerically, the reported plants' peroxides have been classified into seventy-four hydro-peroxides, hundred seven endo-peroxides and eleven acyl-peroxides.  Endo-peroxides (cyclic alkyl peroxides) are an important group due to their high variety of structural frameworks, and we have further divided them into "four-, five-, six and seven"-membered rings. Biosynthetically, a shedding light on the intricate mechanisms behind the formation of plant-derived peroxides are addressed as well.

Antibacterial Potential of Bacterial Cellulose Impregnated with Green Synthesized Silver Nanoparticle Against S. aureus and P. aeruginosa.

In this study, bacterial cellulose (BC) impregnated with green synthesized silver nanoparticles (AgNPs) is evaluated as an antimicrobial membrane for wound-healing treatment. Green synthesized silver nanoparticles using Moringa oleifera leaf extract were characterized using UV‒visible spectroscopy, FTIR, X-ray diffraction, and transmission electron microscopy. The results confirmed that the resulted particles were Ag2O and metallic Ag in nanoscale with an average size ranged from 24 to 40 nm. The green synthesized nanoparticles incorporated within both bacterial cellulose and filter paper discs showed excellent antibacterial activities against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027. There was no significant difference noticed between bacterial cellulose and filter paper holding capacity to nanoparticles and there was lack of interaction between bacterial cellulose and impregnated nanoparticles as elaborated by Fourier transform infrared spectral analyses. Scanning electron microscopy investigation showed major distortions effects of green synthesized silver nanoparticles on bacterial cell morphology.

Utilizing Estra-1,3,5,16-Tetraene Scaffold: Design and Synthesis of Nitric Oxide Donors as Chemotherapeutic Resistance Combating Agents in Liver Cancer.

A new series of nitric oxide-releasing estra-1,3,5,16-tetraene analogs (NO-∆-16-CIEAs) was designed and synthesized as dual inhibitors for EGFR and MRP2 based on our previous findings on estra-1,3,5-triene analog NO-CIEA 17 against both HepG2 and HepG2-R cell lines. Among the target compounds, 14a (R-isomer) and 14b (S-isomer) displayed potent anti-proliferative activity against both HepG2 and HepG2-R cell lines in comparison to the reference drug erlotinib. Remarkably, compound 14a resulted in a prominent reduction in EGFR phosphorylation at a concentration of 1.20 µM with slight activity on the phosphorylation of MEK1/2 and ERK1/2. It also inhibits MRP2 expression in a dose-dependent manner with 24% inhibition and arrested the cells in the S phase of the cell cycle. Interestingly, compound 14a (estratetraene core) exhibited a twofold increase in anti-proliferative activity against both HepG2 and HepG2-R in comparison with the lead estratriene analog, demonstrating the significance of the designed ∆-16 unsaturation. The results shed a light on compound 14a and support further investigations to combat multidrug resistance in chemotherapy of hepatocellular carcinoma patients.

Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies.

New hydrazonoyl-sulfonylthiazoles were designed and synthesized as EGFR inhibitors. The new sulfonylthiazole derivatives were assessed in vitro to measure their effect on EGFR. They revealed marked inhibitory activity against EGFR kinase having IC50 range from 0.037 to 0.317 µM compared to reference drug dasatinib (IC50 = 0.077 µM). Six derivatives of the newly synthesized compounds showed potent inhibitory activity relative to dasatinib. Furthermore, the new hits were examined concerning their cytotoxic effect on human breast cancer cell line (MCF7), hepatic cancer cell line (HepG2) using MTT assay. N-(2-Benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-thiazol-2-yl)-hydrazine (IC50 = 1.24 µM) revealed higher potency than dasatinib (IC50 = 11.6 µM) against MCF7cell line. Besides, N-(2-benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-5-p-tolylazo-thiazol-2-yl)-hydrazine exhibited excellent cytotoxicity against HepG2cell line (IC50 = 3.61 µM), exceeding that of dasatinib (IC50 = 14.10 µM). In addition to low cytotoxic effect on normal (WI-38) cells, describing the high safety profiles of these compounds. Moreover, molecular docking was done in order to determine the possible binding modes of such compounds inside the binding site of EGFR.

The Impact of Optical Coherence Tomography in the Early Identification of Children with Sickle Cell Retinopathy.

Introduction: Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods: This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results: The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion: OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.

Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl-hydrazone derivatives as histone lysine acetyl-transferase inhibitors and apoptosis inducers.

Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol-2-yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti-histone lysine acetyl-transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A-associated protein p300), compared to CPTH2. Among all the tested derivatives, compound 10b revealed the highest activity against both P300 and pCAF. In addition, the new hits were tested for anticancer efficacy against two leukemia cell lines. Most of them showed a moderate to potent antitumor effect on the k562 and CCRF-CEM cell lines. Interestingly, the activity of compound 10b against the k562 cell line was found to be higher than that of CPTH2. Furthermore, it showed a good safety profile, better than CPTH2 on normal cells. Molecular docking analysis was carried out to reveal the crucial binding contacts in the inhibition of the P300 and pCAF enzymes.

Microshear Bond Strength, Ultramorphological, and Elemental Assessment of Gold-Silver Nanoparticle-treated Dentin Bonded to Resin Composite with Different Adhesive Modes.

AIM: The aim of the present study is to evaluate the effect of Ag-Au NPs formulation as surface pretreatment by assessing the microshear bond strength, ultra-morphological, and elemental characteristics of gold-silver nanoparticle-treated dentin to resin composite with different adhesive modes. MATERIALS AND METHODS: A total of 60 extracted sound human permanent molars were selected to test the microshear bond strength of composite resin to dentin (40 teeth) and 20 molars were used to assess the ultramorphological and elemental characteristics of silver-gold nanoparticles using environmental scanning electron microscope (ESEM) with energy-dispersive X-ray (EDX) analyzer. The specimens were randomly divided into two main groups according to measured tests either microshear bond strength or elemental analysis. For the bond-strength testing group, 40 teeth were equally distributed into two main groups (20 each) according to dentin-surface pretreatment with or without the use of silver-gold nanoparticles. Then, each group was further divided into two subgroups (10 specimens for each) according to adhesive mode. For ultramorphological and elemental analysis, 20 teeth were equally divided into similar previously mentioned groups according to treatment modalities (5 teeth per group). The multimode bonding agent used in this study was single-bond universal, 3M. The data were collected and statistically analyzed. The significance level was set at p ≤0.05. RESULTS: The results showed that different etching modes had no statistically significant effect. Also, pretreatment had no statistically significant effect. The interaction between the two variables also had no statistically significant effect. Majority of samples in all groups had mixed failure mode. Ultramorphological examination of the tested samples treated with silver-gold nanoparticles revealed proper dispersion of nanoparticles in dentin. CONCLUSIONS: The new formulation of silver-gold nanoparticles did not interfere with the bond strength and sealing ability of resin composite restoration in different adhesion modes. CLINICAL SIGNIFICANCE: The cavity disinfection with silver-gold nanoparticles did not affect the marginal integrity of resin composite restoration. Further studies should be done to evaluate the impact of application of silver-gold nanoparticles in long duration with other adhesive systems in the clinical scenario.

Mansouramycins E-G, Cytotoxic Isoquinolinequinones from Marine Streptomycetes.

Chemical investigation of the ethyl acetate extract from the marine-derived Streptomyces sp. isolate B1848 resulted in three new isoquinolinequinone derivatives, the mansouramycins E-G (1a-3a), in addition to the previously reported mansouramycins A (5) and D (6). Their structures were elucidated by computer-assisted interpretation of 1D and 2D NMR spectra, high-resolution mass spectrometry, and by comparison with related compounds. Cytotoxicity profiling of the mansouramycins in a panel of up to 36 tumor cell lines indicated a significant cytotoxicity and good tumor selectivity for mansouramycin F (2a), while the activity profile of E (1a) was less attractive.

New Haloterpenes from the Marine Red Alga Laurencia papillosa: Structure Elucidation and Biological Activity.

Analysis of the air-dried marine red alga Laurencia papillosa, collected near Ras-Bakr at the Suez gulf (Red Sea) in Egypt delivered five new halogenated terpene derivatives: aplysiolic acid (1), 7-acetyl-aplysiol (2), aplysiol-7-one (3), 11,14-dihydroaplysia-5,11,14,15-tetrol (5a), and a new maneonene derivative 6, named 5-epi-maneolactone. The chemical structures of these metabolites were characterized employing spectroscopic methods, and the relative and absolute configurations were determined by comparison of experimental and ab initio-calculated NMR, NOE, ECD, and ORD data, and by X-ray diffraction of 2 and 6. The antimicrobial activities of the crude extract and compounds 1-3, 5a and 6 were studied.

Assessment of eye doses to staff involved in interventional cardiology procedures in Kuwait.

In this study, which is the first of its kind in the gulf region, eye doses of interventional cardiologists and nurses were measured using active dosimeters for left and right eyes, in 60 percutaneous coronary interventions in three main hospitals in Kuwait. The dose given in terms of Hp(0.07) per procedure when ceiling suspended screens were used by main operators ranged from 18.5 to 30.3 µSv for the left eye and from 12.6 to 23.6 µSv for the right eye. Taking into account typical staff workload, the results show that the dose limit of 20 mSv/year to the eyes can be exceeded for interventional cardiologists in some situations, which demonstrates the need of using additional effective radiation protection tools, e.g. protective eye spectacles, in addition to the regular and proper use of ceiling suspended screens. With indications of increase in workload, the need for availability of a dedicated active dosimeter for the regular monitoring of eye doses is emphasized.

Antibacterial activities of hexadecanoic acid methyl ester and green-synthesized silver nanoparticles against multidrug-resistant bacteria.

Antibacterial drug resistance is considered one of the biggest threats to human health worldwide, and the overuse of antibiotics accelerates this problem. Multidrug-resistant (MDR) bacteria are becoming harder to treat as the antibiotics used to treat them become less effective. Therefore, it is necessary to evaluate novel methods to control MDR bacteria. In this study, 40 bacterial isolates were collected from diabetic patients. The sensitivity of 40 bacterial isolates to seven antibiotics was evaluated. Four bacterial isolates were resistant to all antibiotic groups. The MDR pathogenic bacteria were selected and identified morphologically and biochemically and confirmed by VITEK® 2 system as follows: Staphylococcus aureus W35, Pseudomonas aeruginosa D31, Klebsiella pneumoniae DF30, and K. pneumoniae B40. Identification of the most resistant P. aeruginosa D31 was confirmed by the sequencing of a 16S ribosomal RNA gene with an accession number (MW241596). The inhibitory activity of eight types of native grown plant extracts against MDR bacteria was studied. Clove alcoholic extract (CAE) showed the highest inhibitory activity against MDR bacteria. Gas chromatography-mass spectrometry analysis of partially purified CAE at 0.9 Rf detected by thin-layer chromatography showed an active compound named hexadecenoic acid methyl ester with the highest antimicrobial effect against clinical pathogenic bacteria. The formation of silver nanoparticles (AgNPs) by CAE was studied. Evaluation of AgNPs was investigated by X-ray diffraction, UV-Vis, and transmission electron microscopy. The antibacterial effect of AgNPs after 2, 4, and 6 days in light and dark conditions was evaluated. Finally, the AgNPs synthesized using CAE possess good inhibition activity against the tested pathogenic bacteria. As a result, the bactericidal components listed above were promising in reducing MDR bacteria and can be used for treatments of bacterial infection and in the development of safe products with a natural base.

Ochraceopyronide, a Rare α-Pyrone-C-lyxofuranoside from a Soil-Derived Fungus Aspergillus ochraceopetaliformis.

The fungal strain was isolated from a soil sample collected in Giza province, Egypt, and was identified as Aspergillus ochraceopetaliformis based on phenotypic and genotypic data. The ethyl acetate extract of the fungal strain exhibited promising activity levels against several pathogenic test organisms and through a series of 1H NMR guided chromatographic separations, a new α-pyrone-C-lyxofuranoside (1) along with four known compounds (2-5) were isolated. The planar structure of the new metabolite was elucidated by detailed analysis of its 1D/2D NMR and HRMS/IR/UV spectroscopic data, while the relative configuration of the sugar moiety was determined by a combined study of NOESY and coupling constants data, with the aid of theoretical calculations. The structures of the known compounds-isolated for the first time from A. ochraceopetaliformis-were established by comparison of their spectroscopic data with those in the literature. All isolated fungal metabolites were evaluated for their antibacterial and antifungal activities against six Gram-positive and Gram-negative bacteria as well as against three human pathogenic fungi.

Production of Terretonin N and Butyrolactone I by Thermophilic Aspergillus terreus TM8 Promoted Apoptosis and Cell Death in Human Prostate and Ovarian Cancer Cells.

The anticancer activity of terretonin N (1) and butyrolactone I (2), obtained from the thermophilic fungus Aspergillus terreus TM8, was intensively studied against prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines. According to this study, both compounds showed potent cytotoxicity towards ovarian adenocarcinoma cells (SKOV3) with IC50 1.2 and 0.6 µg/mL, respectively. With respect to metastatic prostate cells (PC-3), the two compounds 1 and 2 showed a significantly promising cytotoxicity effect with IC50 of 7.4 and 4.5 µg/mL, respectively. The tested fungal metabolites showed higher rates of early and late apoptosis with little or no necrotic apoptotic pathway in all treated prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines, respectively. The results reported in this study confirmed the promising biological properties of terretonin N (1) and butyrolactone I (2) as anticancer agents via the induction of cellular apoptosis. However, further studies are needed to elucidate the molecular mechanism by which cellular apoptosis is induced in cancer cells.

RF-3192C and other polyketides from the marine endophytic Aspergillus niger ASSB4: structure assignment and bioactivity investigation.

Chemical investigation of the methanolic extract of endophytic Aspergillus niger SB4, isolated from the marine alga Laurencia obtuse, afforded the pentacyclic polyketide, RF-3192C (1), the dimeric coumarin orlandin (2), fonsecin B (3), TMC-256A1 (4), cyclo-(Leu-Ala) (5), and cerebroside A (6).The chemical structure of RF-3192C (1) is assigned herein for the first time using 1D/2D NMR and HRESI-MS. Additionally, the revision of the NMR assignments of orlandin (2) was reported herein as well. Investigation of the antimicrobial activities of isolated compounds revealed the high activity of RF-3192C (1) against Pseudomonas aeruginosa and Bacillus subtilis, and moderate activity against yeast. Moreover, an in vitro cytotoxic activity against liver (HEPG2), cervical (HELA), lung (A549), prostate (PC3), and breast (MCF7) cancer cell lines of the isolated compounds was evaluated. The isolation and taxonomical characterization of the producing fungus was reported as well.

Revitalizing operational reliability of the electrical energy system in Libya: Feasibility analysis of solar generation in local communities.

The political upheaval and the civil war in Libya had a painful toll on the operational reliability of the electric energy supply system. With frequent power cuts and crumbling infrastructure, mainly due to the damage inflicted upon several power plants and grid assets as well as the lack of maintenance, many Libyans are left without electricity for several hours a day. As the country has a staggeringly immense potential of solar energy, it is inevitable to exploit such potential, to avert system-wide blackouts. This paper investigates the use of small-scale PV systems in local communities as non-wires alternative (NWA), offering excess energy exchange within local/neighboring microgrids (MGs) for reliable electric power supply. Different combinations of PV/storage/diesel distributed generations (DGs), with grid-interface options, were applied on a case study of a typical dwelling in the Eastern Libyan city of Benghazi. Technical and financial feasibility assessments were carried out to contrast between various supply combinations. Sensitivity analysis of the PV-grid system was also conducted using Net Present Value (NPV) and the payback time indicators to determine the impacts of Feed-in Tariff (FiT) rates, financial incentives, electricity tariff, and inflation rate on the economic viability of the PV grid system. Results show that the PV-grid system has a promising potential under reasonable set of varying system parameters. On top of its social and environmental-friendly advantages, the PV-battery system is found to be more economical when adopted as a standalone NWA solution as compared to the diesel generator option, even at the lowest diesel price. The PV-grid system does not only provide a short-term remedy to the rolling blackouts in Libya but also enhances system operational reliability by providing a NWA to rundown or shattered grid infrastructure, thus bolstering energy provision in residential neighborhoods.

lnc-HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct-acting antivirals therapy.

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.

Diverse bioactive metabolites from Penicillium sp. MMA derived from the red sea: structure identification and biological activity studies.

A soft coral-derived fungus Penicillium sp. among other isolates e high antibacterial, anti-yeast and cytotoxic activities. The fungus, Penicillium sp. MMA, isolated from Sarcphyton glaucoma, afforded nine diverse compounds (1-9). Their structures were identified by 1D and 2 D NMR and ESI-MS spectroscopic data as two alkaloids: veridicatol (1), aurantiomide C (2); one sesquiterpene, aspterric acid (3); two carboxylic acids, 3,4-dihydroxy-benzoic acid; (4) and linoleic acid (5); three steroids, ergosterol (6), ß-Sitosterol (7), ß-Sitosterol glucoside (8) along with the sphingolipid, cerebroside A (9). Biologically, the antimicrobial, antioxidant, in vitro cytotoxicity and antibiofilm activities were studied in comparison with the fungal extract. The in silico computational studies were implemented to predict drug and lead likeness properties for 1-4. The fungus was taxonomically characterized by morphological and molecular biology (18srRNA) approaches.

Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors.

A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f, 4d and 4a against PDE5 were similar to that of sildenafil (100%). These compounds exhibited potent relaxant effects on isolated rat cavernosum tissue with pEC50 values ranging from 8.31 to 5.16 µM. Pyrazolo[3,4-d]pyrimidin-7-one scaffolds have been rationally designed via consecutive molecular modelling studies prior to their synthesis and biological evaluation. In addition, the results of the pharmacophore-based virtual screening revealed that 1v0p_PVB might have promising activity as a PDE-5 inhibitor.