The paths toward non-viral CAR-T cell manufacturing: A comprehensive review of state-of-the-art methods.

Although CAR-T cell therapy has emerged as a game-changer in cancer immunotherapy several bottlenecks limit its widespread use as a front-line therapy. Current protocols for the production of CAR-T cells rely mainly on the use of lentiviral/retroviral vectors. Nevertheless, according to the safety concerns around the use of viral vectors, there are several regulatory hurdles to their clinical use. Large-scale production of viral vectors under "Current Good Manufacturing Practice" (cGMP) involves rigorous quality control assessments and regulatory requirements that impose exorbitant costs on suppliers and as a result, lead to a significant increase in the cost of treatment. Pursuing an efficient non-viral method for genetic modification of immune cells is a hot topic in cell-based gene therapy. This study aims to investigate the current state-of-the-art in non-viral methods of CAR-T cell manufacturing. In the first part of this study, after reviewing the advantages and disadvantages of the clinical use of viral vectors, different non-viral vectors and the path of their clinical translation are discussed. These vectors include transposons (sleeping beauty, piggyBac, Tol2, and Tc Buster), programmable nucleases (ZFNs, TALENs, and CRISPR/Cas9), mRNA, plasmids, minicircles, and nanoplasmids. Afterward, various methods for efficient delivery of non-viral vectors into the cells are reviewed.

Investigation of the performance of a horizontal-axis dual rotor wind turbine.

Recent years have seen a rise in interest in wind energy as a useful alternative to harmful energies like fossil fuels. The dual rotor wind turbine (DRWT) offers more rapid rates of wind energy extraction. The current study intends to compare the performance of the turbine with and without the addition of a second rotor. Additionally, it examines how tip speed ratio and phase shift angle will affect DRWT performance. Realizable k-shear stress transport turbulence models are used to solve the three-dimensional, turbulent, stable, and incompressible flow equations for the performance of dual-rotor wind turbines. Domain-independence tests and an impartial mesh test are run to assess the results and ensure their accuracy. The researcher relies on previous studies while constructing the single rotor wind turbine model. This model uses an S826 airfoil. The front and rear rotors are given streamlined representations using ANSYS, according to the researcher. The independent mesh test indicates that the mesh density has 11.5 million elements. The experiment's results show that the DRWT has a significant effect on the efficiency of wind energy.

Isolation and structural characterization of phytoconstituents from leaves of Bignonia binata.

Phytochemical investigation of Bignonia binata leaves led to the isolation of three new compounds: including a glycoside of simple alcohol, namely binatoside (2), 3,4-dihydroxy-N-methyl piperidin-2-one (7), and a phenyl ethanoid glycoside, namely bignanoside C (8), alongside with five known compounds; including a glycoside of simple alcohol; (2S) propane-1,2-diol 1-O-(6-O-caffeoy1)-ß-D-glucopyranoside (1), phenyl ethanoids; leucosceptoside A (3) and plantainoside C (4), and iridoids; ipolamiide (5) and strictoloside (6). The structure of the isolated compounds was elucidated by various spectroscopic methods, including 1 D and 2 D NMR experiments, HR-ESI-MS as well as by comparison with the literature.

Exploring the Antioxidant Potency of New Naphthalene-Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations.

Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1 H-NMR and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(µM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(µM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2). DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.

A Review: Pharmacological Activity and Phytochemical Profile of Abelmoschus esculentus (2010-2022).

Abelmoschus esculentus L. Moench (okra) which belongs to the family Malvaceae is a commonly consumed vegetable that consists of the seed component which is rich in polyphenolic compounds. The aim of this study is to highlight the chemical and biological diversity of A. esculentus. This plant contains many vitamins, minerals, proteins and carbohydrates in addition to flavonoids, terpenes, phenolic compounds and sterols. These variations in the chemical composition resulted in different therapeutic activities including antidiabetic, hypolipidemic, antioxidant, antimicrobial, anticancer, wound healing, hepatoprotective, immunomodulator, neuroprotective, and gastroprotective activities in addition to cardioprotective activity.

Pharmacological and phytochemical biodiversity of Corchorus olitorius.

Corchorus olitorius L. is a nutritious green leafy vegetable that is eaten as a viscous soup in African and Middle Eastern cultures. The purpose of this review is to highlight the nutritional and nutraceutical potential of this plant. The leaves of C. olitorius are rich providers of minerals as calcium and iron in addition to vitamins B1, B2, folic acid C and E. The leaves contain numerous compounds having several biological effects including antidiabetic and antioxidant properties. Besides, the leaves comprise other phytochemicals such as cardiac glycosides, terpenes, flavonoids, fatty acids, hydrocarbons and phenolics. Various extracts of C. olitorius were shown to exhibit antioxidant, anti-inflammatory, hepatoprotective, antihyperlipidemic, immunostimulant, antitumor, antimicrobial, antidiabetic, analgesic, wound-healing properties and cardioprotective activities.

Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFRwt and aromatase (CYP19A) inhibitors; a study supported by molecular docking.

The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-ß-d-glucopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and clitorin demonstrated the most potent cytotoxic activities with an IC50 of 1.11 ± 0.06 and 2.47 ± 0.14 µM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFRwt kinase inhibition activities with an IC50 of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC50 = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC50 of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC50 = 77.72 ± 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of -4.5287 kcal mol-1 and RMSD value of 1.69 Å. Clitorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of -14.2074 and RMSD value of 1.56 Å. Compounds (1-3) possessed a good bioavailability score with a 0.55 value.

LC-MS-based identification of bioactive compounds and hepatoprotective and nephroprotective activities of Bignonia binata leaves against carbon tetrachloride-induced injury in rats.

The chemical profiling of the main phytoconstituents of total ethanolic extract (TEE) and its different fractions of Bignonia binata leaves was dereplicated using liquid chromatography-high resolution-electrospray ionisation-mass spectrometry (LC-HR-ESI-MS), revealed the presence of various classes of secondary metabolites; eight phenylethanoids, two flavonoidal glycosides and two iridoids. Moreover, the hepatoprotective and nephroprotective activities of the TEE and its different fractions were investigated in carbon tetrachloride (CCl4)-intoxicated rats and were compared with those of silymarin-treated group, revealing the highest potency of the EtOAc group, followed by the aqueous one in improving the CCl4-induced alterations in several biochemical parameters. Besides, EtOAc and aqueous fractions exhibited the most inhibition of CCl4-induced inflammatory mediators and improving the changes in the histopathological structures of the liver and kidney. In addition, the EtOAc fraction demonstrated the highest total phenolic content, whereas TEE showed the highest amount of total flavonoid content.[Formula: see text].

Antiproliferative potential of moluccella laevis L. aerial parts family lamiaceae (labiatae), supported by phytochemical investigation and molecular docking study.

The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 µg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 µg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases. [Formula: see text].

Needlescopic Disconnection and Peritoneal Closure for Pediatric Inguinal Hernia Repair: A Novel Technique.

BACKGROUND: There are many laparoscopic techniques for pediatric congenital inguinal hernia repair. Needlescopic surgery was introduced recently in pediatric patients aiming at getting excellent cosmetic outcomes. PURPOSE: The aim of this study was to describe a novel technique for needlescopic inguinal hernia repair in children. PATIENTS AND METHODS: Needlescopic division of the hernial sac was carried out on 369 children in 6 pediatric tertiary centers during the period from August 2016 to May 2019. All hernias were repaired by a novel needlescopic procedure that replicates all the steps of the open herniotomy. RESULTS: A total of 369 patients with 410 hernias were included in this study. They were 232 (62.9%) males and 137 (37.1%) females, with a mean age of 3.58±1.26 (range=2 to 8 y) and mean internal inguinal ring diameter was 13.65±3.85 mm (range=8 to 20 mm). The mean operative time was 23.36±4.67 minutes for bilateral and 14.28±2.98 minutes for unilateral cases. All cases were completed without conversion to conventional laparoscopy. All cases were followed up for a mean of 19.6±3.2 months. None of our patients developed recurrence or testicular atrophy and the scars were nearly invisible 3 months postoperatively. CONCLUSIONS: Needlescopic pediatric inguinal hernia repair using disconnection of the hernia sac at internal inguinal ring with purse-string suture closure of peritoneum is feasible and safe with no recurrence and with outstanding cosmetic results.

Polyethylene oxide-polyacrylic acid-folic acid (PEO-PAAc) nanogel as a 99m Tc targeting receptor for cancer diagnostic imaging.

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide-polyacrylic acid (PEO-PAAc) nanogel was prepared via γ-radiation-induced polymerization. Variable factors affecting nanoparticles size were investigated. The nanogel was radiolabeled with the imaging radioisotope 99m Tc and finally conjugated with folic acid to target folate receptor actively. PEO-PAAc-folic acid gel was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Biodistribution was studied in normal mice and solid tumor-bearing mice via intravenous and intratumor injections of the radiolabeled PEO-PAAc-folic acid nanogel. Results of biodistribution showed high selective uptake of the prepared complex in tumor muscle compared with normal muscle for both intravenous and intratumor injections. The T/NT ratio was found to be 6.186 and 294.5 for intravenous and intratumor injections, respectively. Consequently, 99m Tc-PEO-PAAc-folic acid complex could be a promising agent for cancer diagnostic imaging.

Needlescopic Appendectomy in Children and Adolescents Using 14-Gauge Needles: A New Era.

Purpose: We are presenting a very minimally invasive technique for laparoscopic appendectomy (needlescopic appendectomy [NAP]) in children and adolescents using suture grasper device, epidural needle, and homemade isolated long diathermy probe without any conventional laparoscopic instruments. Patients and Methods: NAP was attempted in 48 patients with uncomplicated acute appendicitis at Al-Azhar, Tanta University Hospitals and other allied hospitals during the period from May 2017 to November 2018. The study included patients with acute appendicitis and patients scheduled for interval appendectomy. Exclusion criteria were patients with concealed appendix, patients with appendicular abscess or appendicular mass, patients with acute appendicitis complicated with generalized peritonitis, and patients unfit for laparoscopy. The appendix was brought outside through the umbilical port and the operation was completed extracorporeally. In cases of appendicitis with tethered cecum, the whole procedure was completed intracorporeally. Results: Forty-eight patients with acute uncomplicated appendicitis were treated by NAP. They were 36 males and 12 females with a mean age of 9 ± 3.7 years (range = 4-15 years). Two cases with concealed appendix and one case with appendicular mass were diagnosed during initial laparoscopy and excluded from the study. Thirty-two cases (71.11%) were completed intracorporeally and 13 cases (28.89%) were completed by extracorporeal NAP. The mean operative time was 33.29 ± 3.95 minutes (range = 27-40 minutes) for intracorporeal NAP and 20.9 ± 7.01 minutes (range = 14-40 minutes) for extracorporeal NAP. Degrees of cosmetic satisfaction of the patients and parents were excellent in 93.33% (N = 42/45 patients), and very good in 6.67% (N = 3/45 patients) of patients. Conclusion: NAP using needles only is a new technique that is very minimally invasive, very cheap, safe, reproducible, and easy to be done with outstanding cosmetic results.

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Both ethyl acetate and aqueous fractions of Tabebuia aurea leaves exhibited noteworthy antioxidant and nephroprotective activities against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, as evidenced by the remarkable improvements of renal serum biomarkers and histopathological features. Additionally, the ethyl acetate fraction displayed a prominent in vitro antitrypanosomal activity against Trypanosoma brucei; consequently, the leaves were subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, ten metabolites were characterized, mostly dominated by flavonoids. Interestingly, two identified constituents viz., 3,9,12,15-octadecatetraenoic acid (9) and 9,11,13-octadecatrienoic acid (10) are reported firstly herein from the genus Tabebuia. Furthermore, among the dereplicated constituents, rutin (5) and kaempferol 3-O-rutinoside (6) exhibited the highest docking scores as effective antitrypanosomal compounds.

Nanoscale poly(acrylic acid)-based hydrogels prepared via a green single-step approach for application as low-viscosity biomimetic fluid tears.

The present work reports a nanotechnology strategy to prepare a low-viscosity poly(acrylic acid) (PAAc)-based tear substitute with enhanced efficacy and compliance. Specifically, nanogels composed of PAAc and polyvinylpyrrolidone (PVP) were prepared by adapting an ionizing radiation method. For this purpose, different aqueous systems: PVP/PAAc nanoparticulate complexes, PVP/acrylic acid (AAc), N-vinylpyrrolidone (N-VP)/PAAc, and N-VP/AAc were exposed to gamma rays. The dynamic light scattering technique showed that stable nanogels are only produced in a relatively high yield from the PVP/AAc system. Nanogel formation was driven by the hydrogen-bonding complexation between PVP and PAAc (formed in situ) as well as the radiation-induced cross-linking. Transparency, viscosity and mucoadhesiveness of emerged nanogels were optimized by controlling the feed composition and irradiation dose. Furthermore, neutralized nanogels were topically applied in a dry eye model and compared with a PAAc-based commercial tear substitute, namely Vidisic® Gel. The results of Schirmer's test and tear break-up time demonstrated that nanogels prepared from AAc-rich feed solutions at 20 kGy enhanced markedly the dry eye conditions. The histopathological analysis also ensured the competence of PAAc-rich nanogels to completely return the corneal epithelium to its normal state.

Needlescopic Appendectomy in Children and Adolescents Using 14G Needles: A New Era.

Purpose: We are presenting a new very minimally invasive technique for laparoscopic appendectomy (needlescopic appendectomy [NAP]) in children and adolescents using suture grasper device, epidural needle, and homemade isolated long diathermy probe without any conventional laparoscopic instruments. Patients and Methods: NAP was attempted in 48 patients with uncomplicated acute appendicitis at Al-Azhar, Tanta University Hospitals and other allied hospitals during the period from May 2017 to November 2018. The study included patients with acute appendicitis and patients scheduled for interval appendectomy. Exclusion criteria were patients with concealed appendix, patients with appendicular abscess or appendicular mass, patients with acute appendicitis complicated with generalized peritonitis, and patients unfit for laparoscopy. The appendix was brought outside through the umbilical port and the operation was completed extracorporeally. In cases of appendicitis with tethered cecum, the whole procedure was completed intracorporeally. Results: Forty-eight patients with acute uncomplicated appendicitis were treated by NAP. They were 36 males and 12 females with a mean age 9 ± 3.7 years (range = 4-15 years). Two cases with concealed appendix and one case with appendicular mass were diagnosed during initial laparoscopy and excluded from the study. Thirty-two cases (71.11%) were completed intracorporeally and 13 cases (28.89%) were completed by extracorporeal NAP. Mean operative time was 33.29 ± 3.95 minutes (range = 27-40 minutes) for intracorporeal NAP and 20.9 ± 7.01 minutes (range = 14-40 minutes) for extracorporeal NAP. Degrees of cosmetic satisfaction of the patients and parents were excellent in 93.33% (N = 42/45 patients), and very good in 6.67% (N = 3/45 patients) of patients. Conclusion: NAP using needles only is a new technique that is very minimally invasive, very cheap, safe, reproducible, and easy to be done with outstanding cosmetic results.

Novel application of the sewing machine principle; a new simplified intracorporeal suturing technique for pediatric inguinal hernia.

BACKGROUND: The desire of pediatric surgeon to reduce incision related morbidity and pain while achieving good cosmetic results has recently led to the introduction of single incision pediatric endosurgery [SIPES] and needlescopic surgery. Intracorporeal suturing and knot tying during SIPES remain challenging. The aim of this study is to introduce a novel and simple technique for intracorporeal suturing of the pediatric inguinal hernia after needlescopic disconnection of hernia sac using just needles rather than laparoscopic instruments. It is an imitation of the principles of sewing machine. METHODS: The first author discussed the idea of the technique with the coauthors and a demonstration was done on a Silicon Pad before application of the technique on children with congenital inguinal hernia [CIH] for peritoneum closure after needlescopic disconnection of the hernia sac. The main outcome measures were feasibility of the technique, suturing and knotting time and recurrence rate. RESULTS: The sutures were snugly applied to the ridges of Silicon Pad with good approximation and the knot was firmly tightened in all experiments. After applying and mastering the technique on a Silicon Pad, we shifted to use it on 373 children with 491 hernia defects. All operations were completed by the needlescopic technique without the need for insertion of any laparoscopic instruments. The time required for suturing of the peritoneum around internal inguinal ring [IIR] and knot tying, decreased considerably from 6 min 27 s in the first operation to less than 4 min after the fifth operation and stabilized at approximately 4 min 30 s. No major intraoperative complication. There was no recurrence during a mean follow-up period of 19.6 ±â€¯1.2 months. CONCLUSION: The closure of the peritoneum around the IIR using needles mimicking what is happening in sewing machine suturing is a feasible, safe and effective line of treatment of children with CIH. The cosmetic results are 42 outstanding without any recurrence.

Bioactive pyrrole alkaloids isolated from the Red Sea: marine sponge Stylissa carteri.

Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (±) ageliferin and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-) clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z-spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4-bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated derivatives viz., E-debromohymenialdisine and aldisine. The structure elucidations of isolated compounds were based on 1D & 2D NMR spectroscopic and MS studies, as well as by comparison with literature. In-vitro, Z-spongiacidin D exhibited a moderate activity on (ARK5, CDK2-CycA, CDK4/CycD1, VEGF-R2, SAK and PDGFR-beta) protein kinases. Moreover, Z-3-bromohymenialdisine showed nearly similar pattern. Furthermore, Z-hymenialdisine displayed a moderate effect on (ARK5 & VEGF-R2) and (-) clathramide C showed a moderate activity on AURORA-A protein kinases. While, agelongine, (+) manzacidin A, E-debromohymenialdisine and 3,4-dibromo-1H-pyrrole-2-carbamide demonstrated only marginal inhibitory activities. The cytotoxicity study was evaluated in two different cell lines. The most effective secondary metabolites were (+) dibromophakelline and Z-3-bromohymenialdisine on L5178Y. Finally, Z-hymenialdisine, Z-3-bromohymenialdisine and (±) ageliferin exhibited the highest cytotoxic activity on HCT116. No report about inhibition of AURORA-A and B by hymenialdisine/hymenialdisine analogs existed and no reported toxicity of ageliferin existed in literature.

Forsskamide, a new ceramide from aerial parts of Forsskaolea tenacissima Linn.

Although the various folk medicine uses and the biological activity of Forsskaolea tenacissima L., few chemical constituents of this plant have been reported, this provoked us to make our study. Forsskamide, a new ceramide was isolated from aerial parts of F. tenacissima L. (Urticaceae). The chemical structure was established by different spectroscopic methods (1H, 13C-NMR, HMBC, HSQC, ROESY, FAB-MS and HR-FAB-MS). Forsskamide showed a moderate cytotoxic activity by (MTT) method against human colorectal carcinoma cell line (HCT-116) with IC50 33.25 µM in comparison with 5-fluorouracil IC50 26.42 µM. While, it did not show any activity against human hepatocarcinaoma cell line (HepG-2).

Description of D-glucosamine immobilization kinetics onto poly(lactic acid) surface via a multistep physicochemical approach for preparation of novel active biomaterials.

Poly(lactic acid) (PLA) has shown much success in the preparation of tissue engineering scaffolds as it can be fabricated with a tailored architecture. However, the PLA surface has drawbacks including the lack of biofunctional motifs which are essential for high affinity to biological cells. Therefore, this study describes a multistep physicochemical approach for the immobilization of d-glucosamine (GlcN), a naturally occurring monosaccharide having many biological functions, on the PLA surface aiming at enhancing the cell proliferation activity. In this approach, poly(acrylic acid) (PAAc) spacer arms are first introduced into the PLA surface via plasma post-irradiation grafting technique. Then, covalent coupling or physical adsorption of GlcN with/on the PAAc spacer is carried out. Factors affecting the grafting yield are controlled to produce a suitable spacer for bioimmobilization. X-ray photon spectroscopic (XPS) analyses confirm the immobilization of GlcN on the PLA surface. The XPS results reveal also that increasing the yield of grafted PAAc spacer on the PLA surface increases the amount of covalently immobilized GlcN, but actually inhibits the immobilization process using the physical adsorption method. Contact angle measurements and atomic force microscopy (AFM) show a substantial increase of surface energy and roughness of PLA surface, respectively, upon the multistep modification procedure. The cytocompatibility of the modified surfaces is assessed using a mouse embryonic fibroblast (MEF) cell line. Observation from the cell culture basically demonstrates the potential of GlcN immobilization in improving the cytocompatibility of the PLA surface. Moreover, the covalent immobilization of GlcN seems to produce more cytocompatible surfaces if compared with the physical adsorption method. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3176-3188, 2017.

Antifungal potential of marine natural products.

Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source.