Synergism of floated paperboard sludge cake /sewage sludge for maximizing biomethane yield and biochar recovery from digestate: A step towards circular economy.

Anaerobic digestion of floated paperboard sludge (PS) cake suffers from volatile fatty acids (VFAs) accumulation, nutrient unbalanced condition, and generation of digestate with a risk of secondary pollution. To overcome these drawbacks, sewage sludge (SS) was added to PS cake for biogas recovery improvement under a co-digestion process followed by the thermal treatment of solid fraction of digestate for biochar production. Batch experimental assays were conducted at different SS:PS mixing ratios of 70:30, 50:50, 30:70, and 20:80 (w/w), and their anaerobic co-digestion performances were compared to the mono-digestion systems at 35 ± 0.2 °C for 45 days. The highest methane yield (MY) of 241.68 ± 14.81 mL/g CODremoved was obtained at the optimum SS:PS ratio of 50:50 (w/w). This experimental condition was accompanied by protein, carbohydrate, and VFA conversion efficiencies of 47.3 ± 3.2%, 46.8 ± 3.2%, and 56.3 ± 3.8%, respectively. The synergistic effect of SS and PS cake encouraged the dominance of Bacteroidota (23.19%), Proteobacteria (49.65%), Patescibacteria (8.12%), and Acidovorax (12.60%) responsible for hydrolyzing the complex organic compounds and converting the VFAs into biomethane. Further, the solid fraction of digestate was subjected to thermal treatment at a temperature of 500 °C for 2.0 h, under an oxygen-limited condition. The obtained biochar had a yield of 0.48 g/g dry digestate, and its oxygen-to-carbon (O/C), carbon-to-nitrogen (C/N), and carbon-to-phosphorous (C/P) ratios were 0.55, 10.23, and 16.42, respectively. A combined anaerobic co-digestion/pyrolysis system (capacity 50 m3/d) was designed based on the COD mass balance experimental data and biogenic CO2 market price of 22 USD/ton. This project could earn profits from biogas (12,565 USD/yr), biochar (6641 USD/yr), carbon credit (8014 USD/yr), and COD shadow price (6932 USD/yr). The proposed project could maintain a payback period of 6.60 yr. However, further studies are required to determine the associated life cycle cost model that is useful to validate the batch experiment assumptions.

Alginate-modified surfactants functionalized metal-organic framework-based fluorescent film sensors for detection and adsorption of volatile aldehydes in water.

Volatile aldehydes have an adverse impact on both human health and the environment, therefore, a fast, straightforward, highly accurate detection technique for the simultaneous detection and removal of several aldehydes is eagerly anticipated. Herein, novel APGF@ZIF-8 and APOF@ZIF-8 sensing materials were developed by coating fluorescent alginate-modified surfactants (APGF and APOF) into the ZIF-8 MOFs to produce quite porous fluorescent sensors (SBET up to 1519 m2/g). The detection capacity of the prepared sensors for benzaldehyde, glyoxal, formaldehyde, and acetaldehyde has been examined. The detection mechanism was suggested as hydrogen bonding formation between the sensors and volatile aldehydes as confirmed by Gaussian calculations. All the fluorescence spectra of aldehydes display remarkable linear detection relationships in the range of 0.05-200 µM with the limits of detection (LOD) values in the range of 0.001-0.18 µM (0.106-10.44 ppb). These sensors were utilized successfully to detect multiple volatile aldehydes in river water samples with satisfactory recoveries of 96-107 %. Interestingly, fluorescent APGF@ZIF-8/CS and APOF@ZIF-8/CS films as portable disposable removal techniques for benzaldehyde, glyoxal, formaldehyde, and acetaldehyde from water were fabricated. APOF@ZIF-8/CS exhibited an excellent formaldehyde adsorption capacity of 58.30 mg/g and an adsorption removal efficiency of 93.5 %. The adsorption process of biosorbent on various aldehydes was fitted by Freundlich adsorption isotherm. The adsorption kinetics followed Pseudo-second-order kinetic model.

Biosynthesis of MgO Nanoparticles and Their Impact on the Properties of the PVA/Gelatin Nanocomposites for Smart Food Packaging Applications.

Fabricating active and intelligent packaging materials has become the highest demand for catering to market needs, especially after the COVID-19 pandemic, for ensuring food safety. Thus, the wider objective of this article was to promote active and smart packaging biofilms possessing antibacterial and humidity-sensing properties for sustainable poly(vinyl alcohol) (PVA)/gelatin (Ge) reinforced with biosynthesized magnesium nanoparticles (MgO NPs) by a solvent-casting route. The UV-visible spectrum has been utilized to determine the optimized biosynthesized MgO NPs and then the nanostructure of optimized MgO NPs investigated by varying techniques such as XRD, SEM-EDX, TEM, FT-IR, and thermogravimetric analysis. Four MgO NPs proportions (i.e., 1, 3, 5, and 10 wt %) were used to fabricate PVA/Ge biofilms. In the biofilms system, the tensile results showcased that the nanocomposite film containing 5 wt % of MgO NPs had the highest tensile strength value (i.e., 22.10 MPs) compared to the other biofilms or the unfilled blank (i.e., 6.30 MPs). Correspondingly, the humidity-sensing data revealed that the PVA/Ge-1% MgO NPs sensor had higher sensitivity over a broad range of relative humidity from (7-97% RH) and at 100 Hz. Additionally, the hydrophobicity of biofilms, measured by water contact angle, UV-stability, and antioxidant and antibacterial properties was also analyzed to possibly use these biofilms in active food packaging with extended shelf life of foodstuffs. However, the PVA/Ge-1% MgO NPs biofilm was predominately found to possess attractive sensing properties and could be considered as a sensor for intelligent food packaging.

Enhancement of cytotoxic and antioxidant activities of Digenea simplex chloroform extract using the nanosuspension technique.

Digenea simplex (D. simplex), an Egyptian marine red macroalga, contains a diverse group of phytochemicals with unique bioactivities. At the same time, the synthesis of nanosuspension (NS) has received increasing interest to optimize the technological aspects of drugs. Thence, the main objective of this work was to use the chloroform extract (ChlE) of D. simplex to prepare its nanosuspension (ChlE-NS) formulation to increase its aqueous solubility, thereby improving its bioactivity. By using FTIR, GC/MS analysis, and phytochemical screening assays, the chemical profiling of ChlE was assessed. NS was prepared by the antisolvent precipitation technique using 1.5% w/v polyvinyl alcohol (PVA). A light microscope, FTIR, particle size distribution, polydispersity index (PDI), and zeta potential (ZP) measurements was used to characterize the prepared NS. Four cancer cell lines were used in the MTT experiment to investigate the anticancer potential of ChlE and ChlE-NS. An apoptotic mechanism was established using acridine orange/ethidium bromide (AO/EB) dual staining, DNA fragmentation, and increased caspase activity. ChlE and ChlE-NS were also evaluated as antioxidants using DPPH and ABTS free radical assays. The results showed that, when compared to ChlE, ChlE-NS had greater cytotoxic activity against the four cancer cell lines. However, results of antioxidant activity showed that ChlE-NS had an IC50 of 36.86 ± 0.09 and 63.5 ± 0.47%, while ChlE had values of 39.90 ± 0.08 and 86.5 ± 0.8% in DPPH and ABTS assays, respectively. Based on the results of this research, D. simplex ChlE-NS may be an effective strategy for enhancing ChlE's cytotoxic and antioxidant activities.

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia.

Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.

Combined Nasal, Oropharyngeal Povidone Iodine Plus Glycyrrhizic Acid Sprays, Accelerate Clinical and Laboratory Recovery and Reduces Household Transmission of SARS-CoV-2: A Randomized Placebo-Controlled Clinical Trial.

The COVID-19 pandemic is still posing challenging health and economic problems. Effective broad-spectrum antiviral therapy is urgently needed for the control of early SARS-CoV-2 infection to limit its spread and mutations. In this randomized placebo-controlled clinical study, we tested the effects of intranasal and oropharyngeal delivery of a compound of povidone-iodine 0.5% and glycyrrhizic acid 2.5 mg/ml on the laboratory (PCR) and clinical recovery from SARS-CoV-2 patients and their household contacts. 353 patients suspected of having COVID-19 infection were screened by chest CT and nasopharyngeal swab tests (PCR). 200 patients were randomly allocated to two equal groups: treatment and placebo groups. Treatment accelerated the recovery of PCR on days 4, 7, and 10, as evidenced by PCR-positive patients (70, vs. 99%, 20 vs. 65%, 1 vs. 10%) in both the treated and placebo groups, respectively. Treatment enhanced the early recovery of symptoms [day 7.6 ± 2 (CI 7:8.3) vs. 8.9 ± 2 (CI 8.3:9.6)]. Treatment promoted early recovery of anosmia and ageusia [5.6 ± 1 (CI, 4.8:6.4) vs. 11 ± 3 days, (CI, 10.8:12)] in both the treated and control groups (P < 0.0001). There was a notable reduction in transmission of the virus among the household close contacts in the treatment group (4%) vs. 76% in the placebo group. Combined PVI-GA nasal and oropharyngeal spray accelerates both laboratory and clinical recovery of SARS-CoV-2 infected patients in the early phases of the disease and reduces the household spread of the virus; thus, it may play an important role in controlling coronavirus outbreaks. Clinical Trial Registration: https://pactr.samrc.ac.za, PACTR202101875903773.

Cotton bandages finished with microcapsules of volatile organic constituents of marine macro-algae for wound healing.

Microencapsulation is an innovative technique having a growing application in textile finishing. Besides, marine macroalgae contain plenty of phytoconstituents used in various fields especially textile finishing. This work imparts the property of wound healing finish to cotton fabrics producing a bandage from eco-friendly algal volatile organic constituents (VOCs). VOCs extracted from Digenea simplex, Lurencea papillosa, Galaxurea oblongata, and Turbenaria decurrens Egyptian marine macroalgae scattered along the coastline of the Red sea were 0.52, 0.9, 0.87, and 0.62% (v/w), respectively. These VOCs as well as their microencapsulated (VOM) forms were finished onto cotton fabrics by a conventional pad-dry cure technique using sodium alginate (SA) as a shell wall material. The VOCs of each alga were extracted and chemically investigated using gas chromatography coupled with mass spectrometry (GC-MS). The results indicate, in addition to the identification of 125 volatile compounds, the diversity and outstanding differences in volatile composition among the 4 algae. Wound healing activities of the finished fabrics were evaluated. VOCs microcapsules-finished (VOMF) fabrics were more effective compared to VOCs-finished (VOF) fabrics and almost comparable to mebo-ointment (standard drug)-finished (MoF) fabrics. The differences in VOCs efficiencies may be attributable to the diversity in type and amount of volatiles found in the four algae. Therefore, this is a low-cost, convenient, reproducible, and scalable way to obtain encapsulated VOCs for the application in textile wound healing.

New phthalimide analog ameliorates CCl4 induced hepatic injury in mice via reducing ROS formation, inflammation, and apoptosis.

The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.

Production of bioconcrete with improved durability properties using Alkaliphilic Egyptian bacteria.

Microbial-based self-healing of concrete represents innovative technology for improving micro-crack sealing. Microbial bioactivity can induce calcite-precipitation in concrete, which seals micro-cracks. In this respect, two Egyptian bacterial isolates were selected and identified, as Bacillus subtilis (Bs) and Bacillus megaterium (Bm) using MALDI-TOF/MS-Biotyper®. Peak patterns of the bacterial ribosomal proteins showed a high match between samples and standards, which verified species consistency. Bs and Bm were added to the mortar mixture in two concentrations (0.5%, 1%) of cement weight, then the mechanical and physical properties were tested throughout a 180-day time course. The compressive strength of Bm0.5 bacterial mortar samples was increased by 21.4% after 28 days, as compared to control. The rate of water absorption of Bm samples was decreased by 12.4% after 180 days. Bacterial mortar samples showed significant restoration of compressive strength than the original samples by 44%, 21%, and 52.6% for Bs1, Bm0.5, and Bs0.5, respectively. SEM and EDAX analyses confirmed that bacterial samples were denser with fewer voids than the control, as a result of microbial nanosized calcite-precipitation. DTA verified that the amount of CaCO3 and its degree of crystallinity were increased in the bacterial mortar samples. Load-deflection of reinforced-laminates for bacterial mortar samples showed ductile behavior and less deformation as compared to control. In this work, novel concrete with improved mechanical and physical properties has been developed using selected Egyptian microorganisms, it can promote self-healing of micro-cracks with improved durability of the concrete. The application of self-healing bioconcrete can reduce the inspection and maintenance costs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02781-0.

Preparation and characterization of smart therapeutic pH-sensitive wound dressing from red cabbage extract and chitosan hydrogel.

Developing a multifunctional wound dressing that protects, cures and indicates the healing progress, is a new approach of investigation. Red cabbage extract (RCE), consisting of bioactive compounds that have antioxidant, anti-inflammatory, anti-carcinogenic, bactericidal, antifungal, and antiviral activities, was utilized as a natural pH-sensitive indicator. Chitosan-based hydrogel, encapsulating RCE, was developed to obtain a smart therapeutic pH-sensitive wound dressing as antimicrobial bio-matrix provides a comfortable cushion for wound bed and indicates its status. Methacrylated-chitosan was crosslinked by different concentrations of methylenebisacrylamide (MBAA) by which hydrogel mechanical and morphological properties were tuned. The proposed mechanism for hydrogel formation was confirmed by FT-IR. The coloristic properties of the RCE and the changes in color intensity as a function of pH were confirmed by UV-Vis spectroscopy. The effect of MBAA on the mechanical, swelling, release and morphological properties of hydrogel were investigated. MBAA (2.5% wt/v) in 2% wt/v chitosan showed preferable mechanical (20 KPa), swelling (1294% at pH 8 ± 0.2), and release (prolonged up to 5 days) properties. Hydrogel matrices, loaded on cotton gauze submerged in different pH buffer solutions, showed explicit color changes from green to red as pH changed from 9 to 4.

Multifunctional Hydroxyapatite/Silver Nanoparticles/Cotton Gauze for Antimicrobial and Biomedical Applications.

Medical textiles have played an increasingly important protection role in the healthcare industry. This study was aimed at improving the conventional cotton gauze for achieving advanced biomedical specifications (coloration, UV-protection, anti-inflammation, and antimicrobial activities). These features were obtained by modifying the cotton gauze fabrics via in-situ precipitation of hydroxyapatite nanoparticles (HAp NP), followed by in-situ photosynthesis of silver (Ag) NPs with ginger oil as a green reductant with anti-inflammation properties. The HAp-Ag NPs coating provides good UV-protection properties. To further improve the HAp and Ag NPs dispersion and adhesion on the surface, the cotton gauze fabrics were modified by cationization with chitosan, or by partial carboxymethylation (anionic modification). The influence of the cationic and anionic modifications and HAp and Ag NPs deposition on the cotton gauze properties (coloration, UV-protection, antimicrobial activities, and water absorption) was thoroughly assessed. Overall, the results indicate that chemical (anionic and cationic) modification of the cotton gauze enhances HAp and Ag NPs deposition. Chitosan can increase biocompatibility and promotes wound healing properties of cotton gauze. Ag NP deposition onto cotton gauze fabrics brought high antimicrobial activities against Candida albicans, Gram-positive and Gram-negative bacteria, and improved UV protection.

Matrix Metalloproteinase-11 Gene Polymorphisms as a Risk for Hepatocellular Carcinoma Development in Egyptian Patients.

BACKGROUND: Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients. SUBJECTS AND METHODS: Two hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR. RESULTS: Combination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C]. CONCLUSION: Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.

Comparative Molecular Transporter Properties of Cyclic Peptides Containing Tryptophan and Arginine Residues Formed through Disulfide Cyclization.

We have previously reported cyclic cell-penetrating peptides [WR]5 and [WR]4 as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)xC] and linear counterparts (C(WR)xC), where x = 4-5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast carcinoma (MDA-MB-231), and normal kidney (LLCPK) cells after 24 and 72 h incubation. Both cyclic [C(WR)5C] and linear (C(WR)5C) demonstrated comparable molecular transporter properties versus [WR]5 in the delivery of a phosphopeptide (F'-GpYEEI) in CCRF-CEM cells. The uptake of F'-GpYEEI in the presence of 1,4-dithiothreitol (DTT) as the reducing agent was significantly improved in case of l(C(WR)5C), while it was not changed by [C(WR)5C]. Fluorescence microscopy also demonstrated a significant uptake of F'-GpYEEI in the presence of l(C(WR)5C). Cyclic [C(WR)5C] improved the uptake of the fluorescent-labeled anti-HIV drugs F'-d4T, F'-3TC, and F'-FTC by 3.0-4.9-fold. These data indicate that both [C(WR)5C] and linear (C(WR)5C) peptides can act as molecular transporters.

Mucilage-capped silver nanoparticles for glucose electrochemical sensing and fuel cell applications.

A simple, cost-effective and green mucilage-capped silver nanoparticles (Mucilage-AgNPs) modified glassy carbon electrode (GC) composite was constructed for efficient and facile electrochemical oxidation of glucose for the first time. Mucilage-AgNPs were synthesized through the direct chemical reduction of Ag+ by mucilage extracted from Opuntia ficus-indica. Mucilage-AgNPs were identified and characterized using ultraviolet-visible spectroscopy, transmission electron microscopy and square wave voltammetry. Modification of the GC with AgNPs was carried out via a transfer-sticking technique with an immobilization time of 1 h. The Mucilage-AgNPs/GC composite was studied as a possible anode for glucose oxidation in a biofuel cell. The composite resulted in glucose oxidation with a current density and power density of 85.7 µA cm-2 and 25.7 µW cm-2, respectively. Glucose sensing using the Mucilage-AgNPs/GC composite was achieved successfully via two pathways: glucose oxidation and AgNP inhibition. The glucose oxidation-based sensor showed a lower detection limit of 0.01 mM and a linear range of 0.01 to 2.2 mM. The AgNPs inhibition-based sensor provides an indirect determination pathway of glucose with a detection limit of 0.1 mM and a linear range of 0.1 to 1.9 mM. AgNP inhibition is a novel pathway that could be used for determining a large number of organic and inorganic molecules. Overall, the Mucilage-AgNPs/GC is considered a pioneering composite for glucose sensing and fuel cell applications.

Design, synthesis, biological evaluations, molecular docking, and in vivo studies of novel phthalimide analogs.

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53-67% of erythromycin activity on the tested bacteria and 60-70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF-7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad-spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11, which showed good activity toward all the tested cell lines except for MCF-7. The ability of the promising analogs 5, 8, and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase-3 activation and Bcl-2 assay of the best active derivatives 8, 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2.

Lung cancer is one of the major causes of cancer-related mortality worldwide, and non-small-cell lung cancer is the most common form of lung cancer. Several studies had shown that thalidomide has potential for prevention and therapy of cancer. Therefore, the current study aimed to investigate the antitumor effects of two novel thalidomide analogs in human lung cancer A549 cells. The antiproliferative, antimigratory, and apoptotic effects in A549 cells induced by thalidomide analogs were examined. In addition, their effects on the expression of mRNAs encoding vascular endothelial growth factor165 (VEGF165) and matrix metalloproteinase-2 (MMP-2) were evaluated. Their influence on the tumor volume in nude mice was also determined. Results revealed that thalidomide analogs exhibited antiproliferative, antimigratory, and apoptotic activities with more pronounced effect than thalidomide drug. Furthermore, analogs 1 and 2 suppressed the expression levels of VEGF165 by 42% and 53.2% and those of MMP-2 by 45% and 52%, respectively. Thalidomide analogs 1 and 2 also reduced the tumor volume by 30.11% and 53.52%, respectively. Therefore, this study provides evidence that thalidomide analogs may serve as a new therapeutic option for treating lung cancer.

Synthesis and characterization of hydrolysed starch-g-poly(methacrylic acid) composite.

A novel method for the synthesis of starch-g-poly(methacrylic acid) composite was adopted by graft polymerization of hydrolysed starch (HS) and methacrylic acid (MAA) in aqueous medium using an efficient sodium perborate (SPB)-thiourea (TU) redox initiation system. The parameters influencing the redox system efficiency and thence the polymerization method were considered. These parameters comprehended the concentrations of MAA, SPB, TU and SPB/TU molar ratio as well as the polymerization temperature. The polymerization reaction was scrutinized through calculation of the MAA total conversion percent (TC%). The resultant poly(MAA-HS) composite was assessed by evaluating the polymer criteria (the graft yield, GY%; the grafting efficiency, GE%; the homopolymer, HP%; and the total conversion). The comportment of the apparent viscosity of the cooked poly(MAA)-starch composite paste, obtained under diverse polymerization conditions, was examined. Tentative mechanisms, which depict all occasions that happen amid the entire course of the polymerization reaction, have been proffered.

Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

Synthesis and evaluation of thalidomide and phthalimide esters as antitumor agents.

A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.

In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100µM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.