Background Antibiotic resistances of pathogens and breast cancer warrant the search for new alternative strategies. Phytoextracts can eradicate microbe-borne diseases as well as cancer with lower side effects compared to conventional antibiotics. Aim Unripe and ripe Azadirachta indica (neem) seed extracts were explored as potential antibiofilm and anticancer agents in combating multidrug-resistant infectious bacteria as well as anticancer agents against the MDR breast cancer cell lines. Methods Shed-dried neem seeds (both unripe and ripe) were pulverized and extracted using methanol. The chemical components were identified with FTIR and gas chromatography - mass spectrometry. Antibiofilm activity of neem seed extracts were assessed in terms of minimum biofilm inhibitory concentration (MBIC), minimum biofilm eradication concentration (MBEC), and fluorescence microscopic studies on Staphylococcus aureus and Vibrio cholerae. Bacterial cells were studied by fluorescence microscopy using acridine orange/ethidium bromide as the staining agents. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were evaluated to observe the antibacterial activities. Cytotoxicity of the extracts against human blood lymphocytes and the anticancer activity against drug-resistant breast cancer cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence-activated cell sorting (FACS) studies. Results 4-Ethyl-2-hydroxy-2-cyclopentene-1-one, phthalic acid, and 2-hexyl-tetrahydro thiophane were the major compounds in unripe neem seed, whereas 3,5-dihydroxy-6-methyl-2,3-dihydro-4-H-pyran-4-one and 4-ethylbenzamide were predominant in ripe neem seed. Triazine derivatives were also common for both the extracts. MBIC values of unripe and ripe neem seed extracts for S. aureus are 75 and 100 µg/mL, respectively, and for V. cholerae, they are 100 and 300 µg/mL, respectively. MBEC values of unripe and ripe seed extracts are 500 and 300 µg/mL, respectively for S. aureus and for V. cholerae the values are 700 and 500 µg/mL, respectively. Fluorescence microscopic studies at 16 and 24 h, after bacterial culture, demonstrate enhanced antibiofilm activity for the ripe seed extract than that of the unripe seeds for both the bacteria. MTT assay reveals lower cytotoxicity of both the extracts towards normal blood lymphocytes, and anticancer activity against breast cancer cell line (MDA-MB-231) with superior activity of ripe seed extract. FACS studies further supported higher anticancer activity for ripe seed extract. Conclusions Methanolic extract of neem seeds could substantially inhibit and eradicate biofilm along with their potent antibacterial and anticancer activities. Both the extracts showed higher antibiofilm and antibacterial activity against S. aureus (gram-positive) than V. cholerae (gram-negative). Moreover, ripe seed extract showed higher antibiofilm and anticancer activity than unripe extracts. Graphical Abstract
Despite free health care services in Saudi Arabia, the prevalence of caries in children is substantially greater in comparison to other high-income countries. Dental fear in children may be an important issue that needs attention. Therefore, the aim was to investigate the role of dental fear in predicting untreated dental caries in schoolchildren. This analytical cross-sectional study included children aged 8–10 years residing in Saudi Arabia. Dental status via oral examinations was surveyed with the WHO standardized chart and the Children Fear Survey Schedule—Dental Subscale was used to score dental fear. Descriptive, binary, and multivariable logistic regression analyses were performed to report the findings at 5% statistical significance. Overall, there were 798 schoolchildren with an average fear score of 36. Nearly 70.4% reported fear of someone examining their mouth. About 76.9% had at least one carious tooth in their oral cavity. Children with dental fear were 1.8 times (OR = 1.80; 95%CI = 1.26, 2.56) more likely to have at least one untreated carious tooth in their oral cavity than those who did not express fear during oral examinations and dental procedures. Thus, the current study concludes that fear of dentists and dental treatment procedures successfully predicts untreated carious teeth in schoolchildren.
G-Quadruplex, a unique secondary structure in nucleic acids found throughout human genome, elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, RNAs and telomere, G-Quadruplex structure regulates transcription, translation, splicing, etc. Changes in its structure and stability leads to differential expression of oncogenes causing cancer. Thus, targeting G-Quadruplex structures with small molecules/other biologics has shown elevated research interest. Covering previous reports, in this review, we try to enlighten the facts on the structural diversity in G-Quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next-generation cancer treatment.
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