Water soluble curcumin with alkyl sulfonate moiety: Synthesis, and anticancer efficacy.

Curcumin is classified as a chemotherapeutic medication because of its potential against numerous cancer cell lines and ability to inhibit cancer cell proliferation. Despite these findings, curcumin has yet to be commercialized as a drug due to its low water solubility, low absorption, and restricted bioavailability. As a result, there is a demand for water-soluble curcumin with improved solubility, bioavailability, and thus bioactivity. In this study we report the synthesis and the anticancer activities of water-soluble curcumins derivatives with alkyl sulfonate moiety. The target water-soluble curcumin with alkyl sulfonate moieties was created utilizing a straightforward technique that involved reacting curcumin with various sultones. The cytotoxic (24 h) and cytostatic (72 h) anticancer effect on breast carcinoma (MCF-7), liver carcinoma (HepG2), skin melanoma (B16-F110), colon human cancer and HeLa cervical carcinoma cell lines viability % via MTT assay were determined for the prepared derivatives. Results showed that curcumin-derived compounds have a pronounced cytostatic anticancer effect rather than cytotoxic one in relation to the compound type, cancer cell line type, and examined concentration compared to curcumin. The curcumin sulfonates outperformed curcumin activity against the tested cancer cells and showed to be powerful anticancer candidate drugs as supported by the theoretical calculations. This is evident by their high capacity to form H-bonding during docking with the amino acid side chains and the Vina docking score.

Children's rates of COVID-19 vaccination as reported by parents, vaccine hesitancy, and determinants of COVID-19 vaccine uptake among children: a multi-country study from the Eastern Mediterranean Region.

BACKGROUND: Huge efforts are being made to control the spread and impacts of the coronavirus pandemic using vaccines. However, willingness to be vaccinated depends on factors beyond the availability of vaccines. The aim of this study was three-folded: to assess children's rates of COVID-19 Vaccination as reported by parents, to explore parents' attitudes towards children's COVID-19 vaccination, and to examine the factors associated with parents' hesitancy towards children's vaccination in several countries in the Eastern Mediterranean Region (EMR). METHODS: This study utilized a cross-sectional descriptive design. A sample of 3744 parents from eight countries, namely, Iraq, Jordan, Kuwait, Lebanon, Palestine, Qatar, Saudi Arabia (KSA), and the United Arab Emirates (UAE), was conveniently approached and surveyed using Google forms from November to December 2021. The participants have responded to a 42-item questionnaire pertaining to socio-demographics, children vaccination status, knowledge about COVID-19 vaccines, and attitudes towards vaccinating children and the vaccine itself. The Statistical Package for Social Sciences (SPSS- IBM, Chicago, IL, USA) was used to analyze the data. A cross-tabulation analysis using the chi-square test was employed to assess significant differences between categorical variables and a backward Wald stepwise binary logistic regression analysis was performed to assess the independent effect of each factor after controlling for potential confounders. RESULTS: The prevalence of vaccinated children against COVID-19 was 32% as reported by the parents. Concerning parents' attitudes towards vaccines safety, about one third of participants (32.5%) believe that all vaccines are not safe. In the regression analysis, children's vaccination was significantly correlated with parents' age, education, occupation, parents' previous COVID-19 infection, and their vaccination status. Participants aged ≥50 years and those aged 40-50 years had an odds ratio of 17.9 (OR = 17.9, CI: 11.16-28.97) and 13.2 (OR = 13.2, CI: 8.42-20.88); respectively, for vaccinating their children compared to those aged 18-29 years. Parents who had COVID-19 vaccine were about five folds more likely to vaccinate their children compared with parents who did not receive the vaccine (OR = 4.9, CI: 3.12-7.70). The prevalence of children's vaccination in the participating Arab countries is still not promising. CONCLUSION: To encourage parents, vaccinate their children against COVID-19, Arab governments should strategize accordingly. Reassurance of the efficacy and effectiveness of the vaccine should target the general population using educational campaigns, social media, and official TV and radio channels.

New Insights Towards 1,4-Benzodiazepines from Curcumin. Design, Synthesis and Antimicrobial Activities.

BACKGROUND: Curcumin is a safe, versatile natural product with unlimited number of biological activities and a precursor for various heterocyclic compounds. OBJECTIVE: The present study was aimed to the development of a curcumin based antimicrobial reagent with high potency against gram-positive and gram-negative bacteria. METHODS: Herein we report a simple and convenient one step method for synthesizing a series of 1,4-benzodiazepines via condensation cyclization reaction between curcumin and various 1,2- phenylenediamine in refluxed ethanol. RESULTS: A series of new 1,4-benzodiazepins were synthesized and their structures were supported by FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. Synthesized 1,4-benzodiazepins were evaluated for their in vitro antimicrobial activity against gram positive (S. aureus and S. epidermidis) and gram negative (E. coli and P. aeruginosa) bacteria. They exhibited low to high potency against the tested organisms. In particular, dichlorinated 1,4-benzodiazepine 9 exhibited a remarkable potency against the gram-positive bacteria S. aureus (MIC: 3.125 µg mL-1, MBC: 12 µg mL-1). It showed a higher potency than most of the tested reference drugs. Compound 9 showed the medium activity against E. coli. Genotoxic study revealed that, benzodiazepines 9 attacked the DNA of E. coli strains and damaged it. The potency of compound 9, could be attributed to the multiple chlorine atoms present on the aromatic ring. CONCLUSION: Some of the synthesized curcumin based benzodiazepines showed excellent potency against gram positive bacteria. These benzodiazepines could be a great candidate as a future antimicrobial agent.

Genetic diversity of Taenia hydatigena in the northern part of the West Bank, Palestine as determined by mitochondrial DNA sequences.

Cysticercus tenuicollis is the metacestode of canine tapeworm Taenia hydatigena, which has been reported in domestic and wild ruminants and is causing veterinary and economic losses in the meat industry. This study was conducted to determine the sequence variation in the mitochondrial cytochrome c oxidase subunit 1 (coxl) gene in 20 isolates of T. hydatigena metacestodes (cysticercus tenuicollis) collected from northern West Bank in Palestine. Nine haplotypes were detected, with one prevailing (55%). The total haplotype diversity (0.705) and the total nucleotide diversity (0.0045) displayed low genetic diversity among our isolates. Haplotype analysis showed a star-shaped network with a centrally positioned common haplotype. The Tajima's D, and Fu and Li's statistics in cysticercus tenuicollis population of this region showed a negative value, indicating deviations from neutrality and both suggested recent population expansion for the population. The findings of this study would greatly help to implement control and preventive measures for T. hydatigena larvae infection in Palestine.

Molecular detection of nine antibiotic resistance genes in methicillin resistant Staphylococcus aureus isolates.

This study aimed to evaluate the relation between the phenotypic antibiotic susceptibility patterns and the antibiotic resistance genes and to investigate the prevalence of macrolide, lincosamides, streptogramin, aminoglycoside and tetracycline resistance genes among MRSA isolates. A total of 55 clinical MRSA isolates were included in this study, antibiotic resistance was conducted by Kirby-Bauer disk diffusion method, broth microdilution assay and multiplex PCR technique. Our results showed that there was no discordance between conventional susceptibility testing and gene detection by multiplex PCR assay. The prevalence of erm(A), erm(C), tetK, tetM, aacA-aphD, vat(A), vat(B) and vat(C) gene among MRSA isolates was 30.9%, 74.5%, 76.4%, 16.4%, 74.5%, 1.8%, 0% and 5.5%, respectively. These MRSA strains belonged to SCCmec types II, III, IVa and V. Rapid and reliable method for antibiotic susceptibility is important to determine the appropriate therapy decision. Multiplex PCR can be used for confirmation of the results obtained by disk diffusion method or could be used as an alternative diagnostic method in the routine diagnosis for rapid, sensitive, and specific detection of MRSA associated antibiotic resistance genes.

Molecular characterization of Escherichia coli isolates from patients with urinary tract infections in Palestine.

Antibiotic resistance of Escherichia coli isolated from urinary tract infections (UTIs) is increasing worldwide. A total of 41 E. coli isolates were obtained from urine samples from hospitalized patients with a UTI in three hospitals in the northern districts of the West Bank, Palestine during March and June 2011. Resistance rates were: erythromycin (95 %), trimethoprim-sulfamethoxazole (59 %), ciprofloxacin (56 %), gentamicin (27 %), imipenem (22 %), amoxicillin (93 %), amoxicillin-clavulanic acid (32 %), ceftazidime (66 %) and cefotaxime (71 %). No meropenem-resistant isolates were identified in this study. Among the isolates, phylogenetic group B2 was observed in 13 isolates, D in 12 isolates, A in 11 isolates and B1 in five isolates. Thirty-five of the isolates were positive for an extended-spectrum ß-lactamase phenotype. Among these isolates, the blaCTX-M gene was detected in 25, and eight harboured the blaTEM gene. None of the isolates contained the blaSHV gene. Transformation experiments indicated that some of the ß-lactamase genes (i.e. blaCTX-M and blaTEM) with co-resistance to erythromycin and gentamicin were plasmid encoded and transmissible. Apart from this, enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) revealed that the 41 isolates were genetically diverse and comprised a heterogeneous population with 11 ERIC-PCR profiles at a 60 % similarity level.

Molecular characterization of Echinococcus granulosus isolated from sheep in Palestine.

A total of twenty-three Echinococcus granulosus hydatid cysts were collected from infected sheep slaughtered in Nablus abattoir, Nablus - Palestine. Protoscoleces or germinal membranes were used for DNA extraction followed by PCR amplification. Amplified products were analyzed the presence of a fragment of 444bp of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene followed by nucleotide sequencing. Overall, 21 hydatid cysts were positive compared to a negative control. The partial sequences of cox1 gene of E. granulosus strains indicated that the sheep in Palestine were infected with genotype 1 (G1), genotype 2 (G2) and genotype 3 (G3). The prevalence of these genotypes was (14/21) 66.7%, (4/21) 19.0% and (3/21) 14.3% for G1, G2 and G3, respectively. Our results showed that twelve strains of G1 belonged to the common haplotype EG01 which is the major haplotype in all the geographic populations. Phylogenetic analysis also showed that two sequences of G1 genotype which have GenBank accession No. KC109657 and KC109659 were corresponding to G1.4 micro-variants. Only the sequence of GenBank accession No. KC109652 identified in our study as G2 was found to have complete identity to the original sequence described for the cox1 gene (GenBank accession No. M84662). It is concluded that G1 genotype is the predominant genotype in sheep in Palestine. Therefore, these findings should be taken into consideration in developing prevention strategies and control programs for hydatidosis in Palestine.

Molecular analysis and susceptibility patterns of methicillin-resistant Staphylococcus aureus strains causing community- and health care-associated infections in the northern region of Palestine.

BACKGROUND: Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a major global problem. This study attempted to investigate the prevalence of nasal carriage of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) strains among 360 healthy university students at An-Najah National University, Palestine. For the purpose of comparing the staphylococcal cassette chromosome methicillin resistant determinant (SCCmec) type of MRSA, 46 clinical MRSA isolates were also included in this study. METHODS: Susceptibility testing was performed by the disc diffusion method. The genetic association of MRSA isolates was investigated by SCCmec typing. A selected number of isolates were also used to amplify and sequence mecA. RESULTS: Nasal carriage of S aureus was found in 86 of 360 students (24%). MRSA accounted for 9% of S aureus isolates. All 86 strains of S aureus were sensitive to vancomycin. Resistance to penicillin G, amoxicillin/clavulanic acid, ciprofloxacin, erythromycin, and clindamycin was found in 98%, 93%, 33%, 23%, and 12% of the isolates, respectively. Resistance rates of the MRSA isolates were as follows: 100% resistant to penicillin G and amoxicillin/clavulanic acid, 96% to ethromycin, 52% to clindamycin, and 48% to ciprofloxacin. No vancomycin-resistant isolates were identified. In our study, nearly half (52%) of the MRSA isolates belonged to SCCmec types IVa and V. However, SCCmec types II and III are represented by 48%, whereas SCCmec type I was completely absent. CONCLUSION: The findings of this study indicate the existence of SCCmec type IVa in both student nasal carriers and health care settings. This emphasizes the need for implementation of a revised set of control measures in both settings. Moreover, the rational prescription of appropriate antibiotics should also be considered.

Assessment of antifungal activity of herbal and conventional toothpastes against clinical isolates of Candida albicans.

OBJECTIVE: To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans (C. albicans) isolates. METHODS: The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method. Statistical analysis was performed using a statistical package, SPSS windows version 15, by applying mean values using one-way ANOVA with post-hoc least square differences (LSD) method. A P value of less than 0.05 was considered significant. RESULTS: All toothpastes studied in our experiments were effective in inhibiting the growth of all C. albicans isolates. The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient. Antifungal activity of Parodontax toothpaste showed a significant difference (P< 0.001) against C. albicans isolates compared to toothpastes containing sodium fluoride or herbal products. CONCLUSIONS: In the present study, it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C. albicans, while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C. albicans. Some herbal toothpaste formulations studied in our experiments, appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products. Our results may provide invaluable information for dental professionals.

Larval stages of digenetic trematodes in Melanopsis praemorsa snails from freshwater bodies in Palestine.

OBJECTIVE: To detect the species of larval trematodes (cercariae) in Melanopsis praemorsa snails from 5 different fresh water bodies in Palestine. METHODS: A total of 1 880 Melanopsis praemorsa snails were collected from different fresh water bodies in Palestine from October, 2008 to November, 2010. Cercariae in Melanopsis praemorsa snails were obtained by lighting and crushing methods. The behavior of cercariae was observed using a dissecting microscope. RESULTS: Three different species of larval trematodes were identified from Melanopsis praemorsa snails collected only from Al-Bathan fresh water body, while snails from other water bodies were not infected. These species were microcercous cercaria, xiphidiocercaria and brevifurcate lophocercous cercaria. These cercariae called Cercaria melanopsi palestinia I, Cercaria melanopsi palestinia II and Cercaria melanopsi palestinia III have not been described before from this snail in Palestine. The infection rate of Melanopsis praemorsa collected from Al-Bathan fresh water body was 5.7%, while the overall infection rate of snails collected from all fresh water bodies was 4.3%. Details are presented on the morphology and behavior of the cercariae as well as their development within the snail. CONCLUSIONS: These results have been recorded for the first time and these cercariae may be of medical and veterinary importance.

Effect of ethanolic extract of Ecballium elaterium against Staphylococcus aureus and Candida albicans.

OBJECTIVE: To evaluate the antimicrobial activity of ethanolic extract of Ecballium elaterium (E. elaterium) fruits alone against Staphylococcus aureus (S. aureus) strains and Candida albicans (C. albicans) strains, or in combination with penicillin against Staphylococcus areus strains. METHODS: Evaluation of the antimicrobial activity or synergy interaction was carried out using microdilution method. RESULTS: The results showed that ethanolic extract of E. elaterium fruits has antimicrobial activity against methicillin resistant S. aureus (MRSA), methicillin sensitive S. aureus (MSSA) and C. albicans. This extract showed a significant decrease in minimum inhibitory concentrations (MIC) of penicillin against both MRSA and MSSA strains. Fractional inhibitory concentration index (FIC) between penicillin and ethanolic extract of E. elaterium fruits against these test strains was less than 0.5. CONCLUSIONS: This study suggests that ethanolic extract of E. elaterium fruits has antimicrobial activity against S. aureus and C. albicans and there is a possibility of concurrent use of penicillin and E. elaterium extract in combination in the treatment of infections caused by MRSA and MSSA strains. A wider study is needed to identify the effective components, the mode of action and the possible toxic effect in vivo of these ingredients.

Isolation of shiga toxigenic Escherichia coli from raw beef in Palestine.

Shiga toxigenic Escherichia coli (STEC) isolated from raw beef samples in northern Palestine during a 1-year period were characterized for virulence genes by a polymerase chain reaction (PCR) assay and screened for their antibiotic resistance. STEC was identified in 44 (14.7%) of 300 raw beef samples. Twelve (27.3%) of the STEC isolates were serotype O157. Nine of those were isolated during summer. The majority of STEC isolates (70.5%) harbored both stx1 and stx2 genes, while the others harbored either stx1 or stx2. High levels of resistance against different antimicrobial agents were detected. Resistance to at least three drugs was found in 55% of the isolates.