Impact of university students' awareness and attitudes on vaccination practices for human papillomavirus, and perception on self-sampling for cervical cancer screening.

BACKGROUND: The burden of Human Papilloma Virus (HPV)-associated cancer remains high in developing nations. AIMS: To assess the impact of self-reported awareness and attitudes on vaccination practices, and the perception on self-sampling for cervical cancer screening. METHODS: A 12-month survey using purposive sampling of females attending an urban public university was conducted. SPSS version 25 was used to compare the responses for students enrolled in health vs non-health related programmes. RESULTS: Of the 290 questionnaires distributed, 240 were returned (response rate = 83%) in approximately equal proportion from the faculties of Health Science and Pharmacy (n = 127), and from the Hotel and Tourism, Business Management, and Art and Design (n = 113) faculties. About one-third (28.8%) had completed 3 shots, 19.6% received the first shot, 11.4% had scheduled appointments for first shots while 40.2% were both unvaccinated and had not scheduled any appointment. Most (71%) were aware of the HPV vaccines while 50.5% were unaware that HPV vaccines were also available for men. Students enrolled in health-related programmes were 3.2 times more perceptive to the benefits of vaccination particularly in preventing spread to their partners (OR 3.2, 95% CI 1.3-3.41, p = 0.006) than their counterparts. A weak-positive correlation was observed between knowledge and vaccination practices (r = 0.2, p = 0.001). The level of knowledge on HPV and its vaccine was greater for health-related (Mdn = 6.5) than for students of non-health related (Mdn = 1.5) programmes (U = 2790.5, p-value = 0.00). Attitudes towards immunisation were influenced by perceived benefits versus risks for side effects, cost barriers, and influences of primarily their doctors and parents. The study was limited in that relationship statuses were used to estimate sexual history as direct questions were unanswered in the pilot survey. CONCLUSION: HPV vaccine uptake for an immunisation-targeted young female population is low despite moderate knowledge levels. It is plausible that the low rates among females enrolled in particularly the non-health programmes were impacted by misperceived vaccine-associated risks, and misconception that testing and vaccination for HPV and cervical cancer were for those married or sexually active. Self-sampling could offer a potential alternative to sampling via pelvic examination, particularly for societies where premarital sex is seen as a taboo.

A systematic review on chlorine dioxide as a disinfectant.

The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety of chlorine dioxide as a disinfectant. The literature relating to the use of chlorine dioxide as a disinfectant was systematically reviewed in January 2021 using databases such as PubMed, Science Direct, and Google Scholar. Inclusion criteria were studies that investigated the use of chlorine dioxide to assess the efficacy, safety, and impact of chlorine dioxide as a disinfectant. Out of the 33 included studies, 14 studies focused on the disinfectant efficacy of chlorine dioxide, 8 studies expounded on the safety and toxicity in humans and animals, and 15 studies discussed the impact, such as water treatment disinfection using chlorine dioxide. Chlorine dioxide is a safe and effective disinfectant, even at concentrations as low as 20 to 30 mg/L. Moreover, the efficacy of chlorine dioxide is mostly independent of pH. Chlorine dioxide can be effectively used to disinfect drinking water without much alteration of palatability and can also be used to destroy pathogenic microbes, including viruses, bacteria, and fungi from vegetables and fruits. Our review confirms that chlorine dioxide is effective against the resistant Mycobacterium, H1N1, and other influenza viruses. Studies generally support the use of chlorine dioxide as a disinfectant. The concentration deemed safe for usage still needs to be determined on a case-by-case basis.

General Health Benefits and Pharmacological Activities of Triticum aestivum L.

Common wheat (Triticum aestivum), one of the world's most consumed cereal grains, is known for its uses in baking and cooking in addition to its medicinal uses. As this plant's medical benefits are enormous and scattered, this narrative review was aimed at describing the pharmacological activities, phytochemistry, and the nutritional values of Triticum aestivum. It is a good source of dietary fiber, resistant starch, phenolic acids, alkylresorcinols, lignans, and diverse antioxidant compounds such as carotenoids, tocopherols and tocotrienols. These constituents provide Triticum aestivum with a wide range of pharmacological properties, including anticancer, antimicrobial, antidiabetic, hypolipemic, antioxidant, laxative, and moisturizing effects. This review summarized the established benefits of wheat in human health, the mode of action, and different clinical, in vitro and in vivo studies for different varieties and cultivars. This review also gives an insight for future research into the better use of this plant as a functional food. More clinical trials, in vivo and in vitro studies are warranted to broaden the knowledge about the effect of Triticum aestivum on nutrition-related diseases prevention, and physical and mental well-being sustenance.

Estrogenic phytochemical from Labisia pumila (Myrsinaceae) with selectivity towards estrogen receptor alpha and beta subtypes.

Labisia pumila var. alata (Myrsinaceae) or "Kacip fatimah" is a famous Malay traditional herb used for the maintenance of women's health. The extracts of L.pumila displayed estrogenic activity in rats. Nonetheless, the estrogenic bioactives were not identified. The aim of the study is to identify estrogenic compounds contributing to the established estrogenic activity. Bioactivity-guided-isolation method guided the isolation of pure bioactives. The hexane extract was subjected to a series of silica gel flash and open column chromatography with increasing amount of ethyl acetate in hexane or methanol in chloroform. Each fraction or pure compounds were evaluated on it's estrogen receptor (ER) binding activity with the fluorescence polarization competitive ERα and ERß binding assay kit. Cytotoxic assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method was used to establish the cytotoxic activity of the compounds. Four alkyl resorcinols and a dimeric 1,4-benzoquinone, namely belamcandol B (1), 5-pentadec-10'-(Z)-enyl resorcinol (2), 1,3-dihydroxy-5-pentadecylbenzene (3), 5-(heptadec-12'-(Z)-enyl) resorcinol (4) and demethylbelamcandaquinone B (5) were identified with selective binding affinities towards either ERα or ERß exhibiting selectivity ratio from 0.15-11.9. Alkyl resorcinols (2)-(4) exhibited cytotoxic activity towards HL60 cells with IC50 values from 19.5-22.0 µM. Structural differences between compounds influence the binding affinities to ER subtypes. Further study is needed to establish the agonist or antagonist effect of these compounds on various tissues and to identify if these compounds exert cytotoxic activity through the ERs. When consuming L.pumila as a complementary medicine, careful consideration regarding it's estrogenic compound content should be given due consideration.

Safety assessment of standardized aqueous Brucea javanica extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica and its aqueous decoction is a traditional medicine consumed by diabetic patients in Malaysia. The daily consumption of B. javanica seeds and it's aqueous decoction causes much concern as the quassinoids and its glycosides from the seeds exhibited various pharmacological activity at low doses. AIMS OF STUDY: The aim of the present study is to evaluate the repeated dose toxicity of the standardized aqueous extract administered daily for 30 days through oral administration at its effective hypoglycemia doses. MATERIALS AND METHODS: The seeds were dried, ground and extracted in deionized water. A HPLC-photodiode array method was developed and validated for the standardization of both the hypoglycemia agents, namely bruceine D and E in aqueous extract. Both normoglycemia and streptozotocin (STZ)-induced diabetic rats were fed orally with 15, 30 and 60mg/kg body weight of standardized aqueous extract. The blood glucose was measured at 0-8h. In repeated dose toxicity, similar doses were administered orally to rats for 30 days. At the end of 30 days, the blood was withdrawn and subjected to biochemical and haematology analysis while organs were harvested for histology analysis. RESULTS: Oral administration of standardized aqueous extract exhibited a dose-response relationship in both the normoglycemia and STZ-induced diabetic rats. Daily oral administration of 15, 30 and 60mg/kg standardized aqueous extract for 30 days to rats did not show signs to toxicity in its biochemical, haematology and histology analysis. CONCLUSION: In conclusion, although the seeds were reported to contain compounds with various pharmacological activity, the daily oral administration to rats for 30 days do not showed signs of toxicity at its effective hypoglycemia doses.

HPLC-MS/MS method for bioavailability study of bruceines D & E in rat plasma.

Bruceines D and E are quassinoids from seeds of Brucea javanica (L.) Merr. exhibiting hypoglycemia effect. The crude drug is used as a traditional medicine by diabetes patients. The aim of this study is to understand the bioavailability and pharmacokinetics of both the bruceines D & E. A rapid and sensitive HPLC-MS/MS method was developed and validated for the quantification of both quassinoids, bruceines D & E in rat plasma. Both the bruceines D & E were separated with the Zorbax SBC-18 column with gradient elution and mobile phase system of acetonitrile and deionized water with 0.1% formic acid at a flow rate of 0.5mL/min. Analytes were detected in multiple reaction monitoring (MRM) mode with electrospray positive ionization. The quassinoids, namely bruceines D & E were detected with transitions of m/z 411.2→393.2 and m/z 395.2→377.2, respectively. Another quassinoid, eurycomanone was used as the internal standard with transition of m/z 409.2→391.2. The method was validated and conformed to the regulatory requirements. The validated method was applied to pharmacokinetic and bioavailability studies in rats. The pharmacokinetic study indicated both bruceine D and E were rapidly absorbed into the circulation system and reached its peak concentration at 0.54±0.34h and 0.66±0.30h, respectively. Bruceine E was eliminated slower than Bruceine D with t1/2 value almost increased two-fold compared to Bruceine D. In conclusion, a rapid, selective and sensitive HPLC-MS/MS method was developed for the simultaneous determination of both the bruceines D and E in rat plasma. Both bruceines D and E displayed poor oral bioavailability.

In vitro evaluation and in silico screening of synthetic acetylcholinesterase inhibitors bearing functionalized piperidine pharmacophores.

A series of densely functionalized piperidine (FP) scaffolds was synthesized following a diastereoselective one-pot multicomponent protocol under eco-friendly conditions. The FPs were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activity, and in silico studies for all the target compounds were carried out using pharmacophore mapping, molecular docking and quantitative structure-activity relationship (QSAR) analysis in order to understand the structural features required for interaction with the AChE enzyme and the key active site residues involved in the intermolecular interactions. Halogenation, nitration or 3,4-methylenedixoxy-substitution at the phenyl ring attached to the 2- and 6-positions of 1,2,5,6-tetrahydropyridine nucleus in compounds 14-17, 19, 20, 24 and 26 greatly enhanced the AChE inhibitory activity. The docking analysis demonstrated that the inhibitors are well-fitted in the active sites. The in silico studies enlighten the future course of studies in modifying the scaffolds for better therapeutic efficacy against the deadly Alzheimer's disease.

Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death and inflammation.

Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,ß-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition.

Goniolandrene A and B from Goniothalamus macrophyllus.

Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160 µM. Goniothalamin (3) exhibited the highest inhibition of 0.42 µM.

Phytochemical constituents from Cassia alata with inhibition against methicillin-resistant Staphylococcus aureus (MRSA).

The methanolic extract of the leaves of CASSIA ALATA was sequentially partitioned in increasing polarity to afford the hexane, chloroform, butanol and residual extract. Crude extracts were evaluated against MRSA using the agar well diffusion assay. The butanol and chloroform extracts both exhibited inhibition against MRSA with inhibition indexes of 1.03 +/- 0.16 and 0.78 +/- 0.07 at the concentration of 50 mg/mL. The butanol extracts were further purified using silica gel and reverse phase chromatography to afford kaempferol ( 1), kaempferol 3- O-beta-glucopyranoside ( 2), kaempferol 3- O-gentiobioside ( 3) and aloe emodin ( 4). The four constituents showed varying degrees of inhibition against MRSA. Both 1 and 4 exhibited MIC (50) values of 13.0 +/- 1.5 microg/mL and 12.0 +/- 1.5 microg/mL, respectively. The kaempferol glycosides 2 and 3 were less active with MIC (50) values of 83.0 +/- 0.9 microg/mL and 560.0 +/- 1.2 microg/mL, respectively. A free hydroxyl group at C-3 of the flavonol structure is a structural requirement for the inhibition of MRSA.

Vasorelaxant activity of cyclic peptide, cyclosquamosin B, from Annona squamosa.

A cyclic octapeptide, cyclosquamosin B (2), isolated from the seeds of Annona squamosa showed a vasorelaxant effect on rat aorta. It showed a slow relaxation activity against norepinephrine (NE)-induced contractions of rat aorta with/without endothelium. It showed inhibition effect on vasocontraction of depolarized aorta with high concentration potassium, but moderately inhibition effect on NE-induced contraction in the presence of nicardipine. These results showed that the vasorelaxant effect by 2 might be attributed mainly to inhibition of calcium influx from extracellular space through voltage-dependent calcium channels.

Dichotomins J and K, vasodilator cyclic peptides from Stellaria dichotoma.

Two new cyclic peptides, dichotomins J (1) and K (2), have been isolated from the roots of Stellaria dichotoma, and their structures were elucidated by chemical degradation and extensive 2D NMR methods. Dichotomins J (1) and K (2) showed a moderate vasorelaxant effect on rat aorta.

Semisynthetic 15-O-acyl- and 1,15-di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials.

Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.

Antiplasmodial studies of Eurycoma longifolia Jack using the lactate dehydrogenase assay of Plasmodium falciparum.

The roots of Eurycoma longifolia Jack have been used as traditional medicine to treat malaria. A systematic bioactivity-guided fractionation of this plant was conducted involving the determination of the effect of its various extracts and their chemical constituents on the lactate dehydrogenase activity of in vitro chloroquine-resistant Gombak A isolate and chloroquine-sensitive D10 strain of Plasmodium falciparum parasites. Their antiplasmodial activity was also compared with their known in vitro cytotoxicity against KB cells. Four quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (3), 13 alpha(21)-epoxyeurycomanone (4), eurycomalactone (6) and an alkaloid, 9-methoxycanthin-6-one (7), displayed higher antiplasmodial activity against Gombak A isolate but were less active against the D10 strain when compared with chloroquine. Amongst the compounds tested, 1 and 3 showed higher selectivity indices obtained for the cytotoxicity to antiplasmodial activity ratio than 14,15 beta-dihydroxyklaineanone (2), eurycomanol (5), 6 and 7.

The toxicity of some quassinoids from Eurycoma longifolia.

The 50 % aqueous ethanol extract of Eurycoma longifolia Jack (Simaroubaceace) roots was partitioned with diethyl ether, n-butanol and then water. Acute toxicity studies of each fraction on mice administered orally and brine shrimps revealed that the n-butanol fraction was the most toxic. Toxicity-guided chromatographic fractionation of the n-butanol fraction identified eurycomanone as the most toxic component. 13,21-Dihydroeurycoma-none, eurycomanol, longilactone, 14,15 beta-dihydroxyklaineanone and eurycomanol-2- O-beta-glucopyranoside were 2.8, 33, 44, 88.9 and > 100 times less toxic on brine shrimps, respectively. A C 20 -type quassinoid, an alpha,beta-unsaturated ketone in ring A, an exomethylene function at C-13 and an oxymethylene bridge connecting C-8 and C-11 of ring C contributed to increased toxicity.

High performance liquid chromatography analysis of canthinone alkaloids from Eurycoma longifolia.

A reversed phase-high performance liquid chromatography method with a photodiode array detector was developed for the simultaneous determination of three major alkaloids, 9-methoxycanthin-6-one (1), 3-methylcanthin-5,6-dione (2) and its 9-methoxy analogue (3) in Eurycoma longifolia Jack. These alkaloids were easily separated by a gradient elution protocol of 20 - 42 % acetonitrile in 0.1 % acetic acid. Compound 1 showed characteristic absorption at 350 nm only whereas its dione analogues, 2 and 3 displayed strong absorptions at both 350 and 451 nm. The linear calibration ranges were 0.7 - 50 microg x mL(-1) for 1, 1.5-50 microg x mL(-1) for 2 and 3.1 -100 microg x mL(-1) for 3. The recoveries of the three alkaloids were 90.8-101.0% with relative standard deviations from 0.35 to 6.31 % (n = 3). The limits of detection for all the alkaloids were within the range of 0.35 - 0.7 microg x mL(-1). This method was successfully applied to the phytochemical analysis of E. longifolia roots obtained from different sources.