Investigating the Promising Anticancer Activity of Cetuximab and Fenbendazole Combination as Dual CBS and VEGFR-2 Inhibitors and Endowed with Apoptotic Potential.

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine-tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Besides, Ce, Fen, and the combination of them were tested against the VEGFR-2 target receptor, compared to Sorafenib as the standard medication. Moreover, the qRT-PCR technique was used to investigate the levels of apoptotic genes (p53 and Bax) and anti-apoptotic gene (Bcl-2) as well. Also, the effect of Ce, Fen, and the combination of them on the level of ROS was studied. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.

A Comparative Analysis of Marginal Adaptation Values between Lithium Disilicate Glass Ceramics and Zirconia-Reinforced Lithium Silicate Endocrowns: A Systematic Review of In Vitro Studies.

This systematic review aimed to identify and analyze in vitro studies on the marginal adaptation values of computer-aided-design/computer-aided-manufacturing (CAD/CAM) and heat-pressed lithium disilicate glass ceramics and zirconia-reinforced lithium silicates and endocrown restorations. A full literature search was conducted in Web of Science, PubMed/Medline, EMBASE, Scopus, Cochrane Library, Google Scholar, and ProQuest electronic databases. The following keywords: endocrown [(marginal adaption) or (marginal fit) or internal fitting)], endocrown [(molar(s)) or (premolar(s) or (posterior teeth) or (maxillary arch) or (mandibular arch)] and ceramic materials as [(lithium disilicate glass ceramic CAD/CAM) or (zirconia) or (heat-press)] were used. Articles were manually searched utilizing their reference lists. Study selection was restricted or limited to the time of publication but not to the type of tested teeth or ceramic material, endocrown design, system of endocrown construction, abutment scanning, and system of the marginal adaption measurement. A total of 17 in vitro studies published between 2016 and 2023 were included in this systemic review. Less than half of the studies were published during 2023. Most studies used lithium disilicate glass ceramic and zirconia-reinforced lithium silicate all-ceramic materials by CAD/CAM or heat-press systems. Marginal adaptation, or marginal gap, was almost equal in the 2 materials, while it was slightly or marginally higher in the heat-press than in the CAD/CAM system. All-ceramic lithium disilicate glass ceramic and/or zirconia endocrowns fabricated for posterior teeth in both arches using CAD/CAM or heat-press had recorded marginal adaptation values within an acceptable range.

Chloroacetonitrile reduces rat prenatal bone length and induces oxidative stress, apoptosis, and DNA damage in rat fetal liver.

One of the disinfection byproducts of chlorinating drinking water is chloroacetonitrile (CAN). Thirty-six female rats were used and distributed equally into four groups. The low dose treated group received CAN at a dose of 5.5 mg/kg body weight/day (1/40 LD50 ) orally from the 6th to 12th day of gestation. The high dose treated group received 11 mg/kg body weight/day (1/20 LD50 ) of CAN orally for the same period, the vehicle control group received 1 mL of corn oil, and the water control group received 1 mL of distilled water orally for the same period. High dose exposure to CAN significantly reduced gravid uterine weight, fetal body weights, and length, and caused obvious skeletal deformities, weak mineralization. Fetal tibial growth plates displayed histopathologic changes. Induced oxidative stress and redox imbalance in fetal liver tissues was evidenced by significantly decreased in catalase and superoxide dismutase activity, and elevated malondialdehyde levels. Histopathological, glycogen content changes, and DNA damage were observed in the fetal liver of high dose treated group. Additionally, administration of high dose of CAN induced apoptosis, evidenced by increased caspase-3 concentration in fetal liver. Thus, extensive exposure to CAN induces poor pregnancy outcomes. CAN levels in water should be monitored regularly.

Polycyclic aromatic hydrocarbons (PAHs) in Greater Cairo water supply systems.

Polycyclic aromatic hydrocarbons (PAHs) pose a constant threat to the environment and public health. There are numerous activities in the Greater Cairo area that emit and release significant amounts of PAHs. Concentrations of these PAHs are released into the air and mixed with surface water, limiting its use. In this study, 17 PAH compounds are mapped at eight sites along the Nile River and its tributaries in Greater Cairo. In addition, their removal efficiency is evaluated with the conventional treatment in eight water treatment plants. PAHs were analyzed using GC-MS from January to December 2018. Naphthalene, anthracene, fluorene, pyrene, and phenanthrene were detected. The total amount of PAHs in raw water was highest in Shamal Helwan (1,325 ± 631 ng/l) and lowest in Mostorod (468 ± 329 ng/l), and the removal ranged from 25 to 31%. Further research is needed to integrate other techniques to reduce PAHs using the conventional treatment, and more efforts should be made to reduce the presence and release of PAHs in raw water.

Aluminum sulfate regeneration from surface water treatment waste in Cairo, Egypt.

The world needs to adapt to recycling and reusing water due to limited resources. So, decision-makers and policy leaders should use sustainable practices to improve protection and pollution remediation. Aluminum sulfate is used for surface water treatment, which leads to waste sludge being disposed into water bodies, causing environmental pollution. Coagulants' regeneration from sludge improves water quality and reuse options. Organics accumulation is the primary concern regarding coagulant regeneration, using acidification. Our study investigated the raw water quality, aluminum sulfate, and sludge and evaluated its influence on coagulant recovery, using acidification, from eight water treatment plants (WTPs) in Cairo, Egypt. The significant elements in the tested sludge were aluminum with a concentration range of 86.65-688.85 mg/g sludge in El-Rawda and Embaba and iron with a concentration range of 9.45-7.45 mg/g in Shamal Helwan and El-Fostat. Recovery percentages of aluminum, iron, manganese, and strontium recorded the highest values 97%, 89%, 89%, and 92% for Embaba, Rod El-Farag, Embaba, El-Rawda, respectively. The correlation between metal concentration and recovery was insignificant in the studied matrix and conditions for the four metals. Total organic carbon (TOC) transfer into recovered solutions was maximum in El-Fostat (82.6%) and minimum in Embaba (36.7%). The TOC transfer percentage depends on the matrix of the sludge. The best location for coagulant recovery is at the Embaba WTP, where there were minimum organics transfer and maximum Al recovery.

Repeated Aluminum Sulfate Recovery from Waterworks Sludge: A Case Study in El-Sheikh Zaid WTP.

Although surface water treatment presents a good solution for pollutants in rivers and freshwater lakes, the purification process itself presents a great threat to the aquatic environment through aluminum waste disposal. Recent studies have introduced coagulants recovery from treatment sludge as a green solution for waste handling and cost reduction. This article aims to evaluate repeated aluminum coagulants recovery from sludge using sulfuric acid. The waste from El-Sheikh Zaid Water Treatment Plant (ESZ-WTP) was characterized, then sequential coagulants recovery using optimum conditions was conducted. In addition, treated water was analyzed to determine the efficiency of the obtained coagulants and their influence on treated water quality. Sequential coagulants recovery using acidification revealed that no metals accumulation took place in the produced coagulants until the third recovery from ESZ-WTP sludge. On the other hand, a noticeable increase in trihalomethanes was detected in the treated water, especially using the third recovered coagulant. In conclusion, sequential coagulants recovery and usage in water treatment is an attractive alternative for single-use original coagulant in ESZ-WTP but for no more than three sequential recoveries. It is advisable to apply a fresh coagulant every three sequential recoveries to enrich the aluminum content and regenerate the sludge before restarting the recovery process.

Evaluation of leached metals in recovered aluminum coagulants from water treatment slurry.

The water treatment industry consumes large quantities of coagulant and produces huge amounts of slurry. The cost of alum used in water treatment, stringent regulations and negative impacts of sludge disposal are the motive to do integrated research studies on the technical feasibility of aluminum coagulant recovery from sludge using acidification. This work studied the leaching of iron, manganese, and chromium as the most extracted metals with aluminum during sludge acidification; furthermore, these metals have a great impact on the recovered coagulants' efficiency and treated water quality. The sludge used was collected from El-Sheikh Zayd water treatment plant in Egypt, then dried and ground; afterward, the effect of acid concentration, sludge mass, temperature, mixing speed and mixing time was studied. In addition, it was noticeable that the efficiency of sulfuric acid in leaching iron, manganese and chromium is higher than that of hydrochloric acid. Also, higher leaching for the three metals was obtained in all the experiments using higher acid concentration, elevated temperature, and rotational speed. Finally, the leached metals in recovered aluminum coagulants will not limit its application to water and wastewater treatment, as their concentrations are still very low if compared with aluminum, even with the highest leaching efficiency.

An optimized approach for simultaneous horizontal data fragmentation and allocation in Distributed Database Systems (DDBSs).

With the substantial ever-upgrading advancement in data and information management field, Distributed Database System (DDBS) is still proven to be the most growingly-demanded tool to handle the accompanied constantly-piled volumes of data. However, the efficiency and adequacy of DDBS is profoundly correlated with the reliability and precision of the process in which DDBS is set to be designed. As for DDBS design, thus, several strategies have been developed, in literature, to be used in purpose of promoting DDBS performance. Off these strategies, data fragmentation, data allocation and replication, and sites clustering are the most immensely-used efficacious techniques that otherwise DDBS design and rendering would be prohibitively expensive. On one hand, an accurate well-architected data fragmentation and allocation is bound to incredibly increase data locality and promote the overall DDBS throughputs. On the other hand, finding a practical sites clustering process is set to contribute remarkably in reducing the overall Transmission Costs (TC). Consequently, consolidating all these strategies into one single work is going to undoubtedly satisfy a massive growth in DDBS influence. In this paper, therefore, an optimized heuristic horizontal fragmentation and allocation approach is meticulously developed. All the drawn-above strategies are elegantly combined into a single effective approach so as to an influential solution for DDBS productivity promotion is set to be markedly fulfilled. Most importantly, an internal and external evaluations are extensively illustrated. Obviously, findings of conducted experiments have maximally been recorded to be in favor of DDBS performance betterment.

Utilization of Drinking Water Treatment Slurry to Produce Aluminum Sulfate Coagulant.

In Egypt, water treatment consumes about 365 000 tons of aluminum sulfate and produces more than 100 million tons of sludge per year. The common disposal system of sludge in Egypt is to discharge it into natural waterways. Toxicity of aluminum, environmental regulations and costs of chemicals used in water treatment and sludge treatment processes led to an evaluation of coagulant recovery and subsequent reuse. The present work aimed at aluminum recovery from sludge of El-Shiekh Zayd water treatment plant (WTP) to produce aluminum sulfate coagulant. Sludge was characterized and the effect of five variables was tested and the process efficiency was evaluated at different operating conditions. Maximum recovery is 94.2% at acid concentration 1.5 N, sludge weight 5 g, mixing speed 60 rpm, temperature 60 °C and leaching time 40 min. Then optimum conditions were applied to get maximum recovery for aluminum sulfate and compared to commercial coagulant on raw water of El-Shiekh Zayd (WTP).

Synthesis, biological evaluation, and molecular docking studies of new pyrazol-3-one derivatives with aromatase inhibition activities.

A new series derived from 4-(2-chloroacetyl)-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one was synthesized, characterized and its pharmacological activity toward aromatase enzyme inhibition was screened and compared to the reference native ligand letrozole. The most active compound of the series was 16, showing IC50 value of 0.0023 ± 0.0002 µm compared to letrozole with IC50 of 0.0028 ± 0.0006 µm. In addition, compounds 26 and 36 exhibit good inhibition activities close to letrozole with IC50 values 0.0033 ± 0.0001 and 0.0032 ± 0.0003 µm, respectively. Moreover, molecular docking studies were conducted to support the findings.

Novel Benzo[d]imidazole-based Heterocycles as Broad Spectrum Anti-viral Agents: Design, Synthesis and Exploration of Molecular Basis of Action.

The design and synthesis of a novel series of benzo[d]imidazole-based heterocycles and their biological evaluation as antiviral agents are reported herein. 1-(1-Methyl-1H-benzo[d]imidazol- 2-yl)-2-thiocyanatoethanone 2 was used as a key intermediate for the synthesis of the thiazolylhydrazine 4, the thiazolylamine 5 and the methylthiazole 7. Coupling of compounds 5 or 7 with the appropriate diazotized aromatic amines gave the diazenyl derivatives 6a-c and 8a-c, respectively. The quinazoline derivative 12 was also synthesized. On the other hand, the phenylthio 20 and the phenylsulphonyl 22 bioisosteresand their respective diazenyl derivatives 21a-c and 23a-c were prepared. The synthesized compounds were evaluated for their HIV-1, HCV, SSPE and H1N1 inhibitory activities and were found to display very promising results. Furthermore, to investigate the underlying possible mechanism of action, in vitro and in silico screening of this series of benzo[d]imidazoles was performed against the viral enzymes HIV-1 RT, HCV NS3/4A serine protease and H1N1 NA1. Overall findings of the executed investigations highlight these novel compounds as very promising potent, broad spectrum antiviral agents.

Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives.

Treatment of 3-phenyl-1,3-thiazolidin-4-one derivative 1 with phenylisothiocyanate in DMF, in the presence of potassium hydroxide, at room temperature gave the non-isolable potassium salt 2. The in-situ reaction of 2 with differently substituted N-aryl hydrazonoyl chlorides 3, 7a-d and 14a-d afforded the corresponding 2-(pyrazolyl)thiazolylimino-5-(thiadiazolylidene)thiazolidin-4-one derivatives 6, 10a-d and 17a-d, respectively. Reaction of 2 with further α-haloketones yielded the 4-(pyrazolyl)thiazolylimino-bis-thiazolidine derivatives 22, 25 and 26. Single crystal X-ray analysis was used in structure elucidation of the products. The in-vitro antiviral screening against four viruses (Poliovirus, Influenza A (H1N1) virus, Hepatitis B virus and Hepatitis C virus) for the obtained compounds was examined. Structure activity relationship (SAR) was also studied. The goal of the work was achieved in discovering a very active compound 10a as anti HCV agent (EC50 0.56 µM).

Novel 4-heteroaryl-antipyrines as DPP-IV inhibitors.

Type 2 diabetes mellitus is a vast growing progressive disease that almost affects one person among every twelve globally. Regardless the availability of wide variety of oral hypoglycemics, only one-third of patients achieves proper glycemic control. With the advantage of the low risk of hypoglycemia, DPP-IV attracted the attention of medicinal chemists as a new target for oral hypoglycemics. In this report, a lead compound 1, with antipyrine scaffold, was obtained, and its binding mode was calculated. Several derivatives with bridged nitrogenous heterocycles have been synthesized via multicomponent reaction under controlled microwave heating conditions. The antidiabetic activity versus DPP-IV protein was evaluated and compared with sitagliptin. Compounds with smaller- or medium-sized nitrogenous bridges were comparable with sitagliptin in terms of DPP-IV inhibitory activity, potentially via targeting Glu203 and Glu204. The oral hypoglycemic activities of compounds with submicromolar IC50 values were further evaluated using diabetic mouse model.

Diphenylpyrroles: Novel p53 activators.

Cellular tumor antigen p53 is crucial for cancer prevention via different mechanisms. E3 ubiquitin-protein ligase HDM2 binds to p53, blocks its ability to activate transcription, and therefore acts as a negative regulator. Blocking p53 binding site on HDM2 was believed to generate efficient antitumor agents. So far, limited scaffolds were reported with HDM2 antagonist activity. Herein, diphenylpyrroles were introduced and evaluated as a novel scaffold in the field of p53 activators. An efficient synthesis of novel 3-heteroaryl-pyrroles is described via reactions of E-3-(dimethylamino)-1-(2-methyl-4,5-diphenyl-1H-pyrrol-3-yl)prop-2-en-1-one or E-1-(2-methyl-4,5-diphenyl-1H-pyrrol-3-yl)-3-morpholinoprop-2-en-1-one with hydrazine hydrate, phenyl hydrazine, hydroxylamine, various heterocyclic amines and active methylene compounds.

Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents.

N-(4-(Pyrazol-4-yl)thiazol-2-yl)-N'-phenylthiourea derivative 2 was synthesized and then treated with variety of hydrazonoyl chlorides under basic condition at reflux to afford the corresponding 2-(4-(pyrazol-4-yl)thiazol-2-ylimino)-1,3,4-thiadiazole derivatives 6, 10a-e and 17a-e. Reaction of 2 with ethyl chloroacetate and with 3-chloro-2,4-pentanedione gave the thiazolidin-4-one 22 and 1,3-thiazole 25 derivatives, respectively. Condensation of thiazolidin-4-one 22 with aldehydes gave their 5-arylidene derivatives 23a-f. Most of the synthesized compounds were tested for anticancer activity against human hepatocelluar carcinoma HepG2, human breast cancer MCF-7 and human lung cancer A549. Their SAR was studied and variously affected by the electronic factor of electron donating and withdrawing groups. Many of the tested compounds showed moderate to high anticancer activity.

Ultrasound assisted one-pot, three-components synthesis of pyrimido[1,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines: A new access via phenylsulfone synthon.

A simple, facile, efficient and three-components procedure for the synthesis of pyrimido[1,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines utilizing phenylsulfone synthon, under ultrasonic irradiation was developed.

Synthesis, spectral characterization, solution equilibria, in vitro antibacterial and cytotoxic activities of Cu(II), Ni(II), Mn(II), Co(II) and Zn(II) complexes with Schiff base derived from 5-bromosalicylaldehyde and 2-aminomethylthiophene.

Schiff base namely 2-aminomethylthiophenyl-4-bromosalicylaldehyde (ATS)(4-bromo-2-(thiophen-2-yl-imino)methylphenol) and its metal complexes have been synthesized and characterized by elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance, mass spectra, ESR and thermal analysis (TGA). The analytical data of the complexes show the formation of 1:2 [M:L] ratio of the formula [ML2], where M represents Ni(II), Zn(II) and Cu(II) ions, while L represents the deprotonated Schiff base. IR spectra show that ATS is coordinated to the metal ions in a bidentate manner through azomethine-N and phenolic-oxygen groups. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria. A cytotoxicity of the compounds against colon (HCT116) and larynx (HEP2) cancer cells have been studied. Protonation constants of (ATS) ligand and stability constants of its Cu2+, Co2+, Mn2+, Zn2+ and Ni2+ complexes were determined by potentiometric titration method in 50% (v/v) DMSO-water solution at ionic strength of 0.1 M NaNO3.

Flow injection spectrofluorimetric determination of iron in industrial effluents based on fluorescence quenching of 1-naphthol-2- sulfonate.

A sensitive and selective spectrofluorimetric method has been developed for flow injection analysis (FIA) of iron(III) based on its fluorescence quenching effect on the water soluble 1-naphthol-2-sulfonate. The fluorescence emission spectra were collected with excitation at 283 nm. The emission peaks of the neutral and anionic forms of 1-naphthol-2-sulfonate as well as the band area were found to decrease linearly with iron(III) concentrations over the range 0.1-18 µg ml(-1) and a detection limit of 3.4 ng ml(-1) (emission at 349 nm) with FIA. Possible interferences from different cations and anions, which could affect the analytical response, are evaluated and showed the high selectivity of the method. The effect of solution pH and 1-naphthol-2-sulfonate concentration were examined and the reaction conditions are optimized. The method is successfully applied to determine iron(III) in industrial effluents from different sources without any complications with recoveries of almost 100% with both manual and flow injection methods. Results were found to be very consistent with those obtained using atomic absorption spectrometry.

Improvement in medically certified death: results from a pilot study in the state of malacca, malaysia.

A systematic approach to death registration and reporting is essential for studies and comparison within or between countries. One of the accepted methods in the system is to have medically certified death. The objective of this study was to improve the proportion of medically certified death (MCD) in the state of Malacca. Structured questionnaires were used by Medical Assistants (MAs) in the investigation of the cause of death for non-medically certified deaths. Data on certification of death by MAs in Malacca was analysed and compared with the total deaths obtained from the Department of Statistics. Possible determinants of deaths were investigated. Total deaths in the state of Malacca during the study period from 2000 - 2001 were 5941. About 35% (883/2493) of the total deaths in year 2000 and 45% (1550/3448) in 2001 certified by MAs were examined. By districts, 50.6% were certified in the district of Malacca Tengah, 13.4% Jasin and 36.0% Alor Gajah in 2000; 65.9% occurred in Malacca Tengah, 11.0% Jasin and 23.2% Alor Gajah in 2001. This project helped to increase the percentage of the medically certified deaths in Malacca from 49.8% in year 1998, 49% in 1999 to 73% in 2000 and 85% in 2001. The proportion of MCD in Malacca in 2000 (73%) may be increased to 93% if all MCDs done by MAs were accepted by the Department of Statistics. There is still a high proportion (23.6%) of ill-defined conditions such as old age and sudden death being diagnosed by MAs. The study shows that the quality of mortality data particularly in the percentage of medically certified deaths can be improved.

Design, synthesis and structure-activity relationship study of novel pyrazole-based heterocycles as potential antitumor agents.

The versatile hitherto unreported 3-[(E)-3-(dimethylamino)acryloyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (3) was prepared via the reaction of 3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) with dimethylformamid-dimethylacetal (DMF-DMA). The latter product and 3-((E)-3-morpholin-4-yl-acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (4) underwent regioselective 1,3-dipolar cycloaddition with nitrilimines to afford the corresponding pyrazole derivatives. In vivo anti-estrogenic activity and acute toxicity after single oral dose of the newly synthesized compounds were evaluated. In vitro disease-oriented primary antitumor screening utilizing 14 cell lines of breast and ovarian tumor subpanels has been also carried out. All tested compounds showed anti-estrogenic properties equipotent or superior to the reference drug, letrozole. 3-[3-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-yl)-1-(4-methylphenyl)-1H-pyrazole-4-carbonyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (27c) and 3-(3-acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (8a) showed a significant cytotoxic activity in a nanomolar range against certain types of breast and ovarian tumors with tolerable toxicity.