2,334 research outputs found
Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea
ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK
Treatment optimisation of multidrug-resistant tuberculosis
A successful treatment outcome is seen in only 60% of persons treated for multidrugresistant
tuberculosis (MDR-TB) worldwide, defined as resistance to both rifampicin and
isoniazid. To improve these disturbingly low numbers, treatment optimisation is highly
needed. Therefore, this thesis will evaluate how to optimise a treatment regimen using
both older and repurposed drugs in studies on regimen composition, resistance
detection, target attainment for efficacy, and reduction of adverse drug reactions.
In the first retrospective observational study (study I), we evaluated the effect of
pyrazinamide treatment on end-of-treatment outcomes in a cohort (n=508) of persons
affected by MDR-TB in Karakalpakstan, Uzbekistan. We found no evidence (aOR 0.86,
95% CI 0.51-1.44, p=0.6) that pyrazinamide treatment was associated with end-oftreatment
outcomes. In study II, pyrazinamide treatment was evaluated using time to
sputum culture conversion in a historical Swedish MDR-TB cohort (n=157). We found
strong evidence that no pyrazinamide treatment compared to receiving pyrazinamide
treatment was associated with a longer time to sputum culture conversion (aHR 0.49,
95% CI 0.29-0.82, p=0.007), when accounting for genotypic drug susceptibility testing
(DST).
In study III, we assessed the total exposure of moxifloxacin and levofloxacin over the
minimum inhibitory concentration of the infecting Mycobacterium tuberculosis strain in
persons with MDR-TB in Xiamen (n=32), China. In this prospective observational study,
we showed that no participants treated with levofloxacin, and 60-73% receiving
moxifloxacin, reached the proposed efficacy targets when dosed according to the
Chinese national guidelines. In the last retrospective observational study (study IV), we
evaluated risk factors for adverse drug reactions associated with linezolid treatment
(n=132) for MDR-TB in Sweden. We found strong evidence that a daily linezolid dose of
≥12 mg/kg was associated with a higher risk of peripheral neuropathy (aHR 2.92, 95% CI
1.09-7.84, p=0.033), anaemia, or leukopenia. Moreover, in an exploratory analysis, a
linezolid trough concentration of ≥2 mg/L was associated with a higher risk of anaemia
and thrombocytopenia.
In conclusion, treatment with pyrazinamide seems to have a role in MDR-TB, at least in
terms of improving interim outcomes. The use of genotypic DST is highly promising and
may simplify and shorten the time to resistance testing. Adequate dosing of
fluoroquinolones is important as underdosing could reduce treatment effects. Linezolid
dose adjustment based on weight, or a high trough level might avoid adverse drug
reactions. Importantly, dose adjustment needs to consider both efficacy and risk of
adverse drug reactions, therefore, therapeutic drug monitoring can be a useful tool in
the quest to personalise treatment
Flavonol Glucosylation: A Structural Investigation of the Flavonol Specific 3-O Glucosyltransferase Cp3GT
Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin cleavage site was incorporated proximal to the tag, followed by cloning in Pichia pastoris, methanol-induced expression, and cobalt-affinity chromatography for initial purification stages. Notably, the recombinant tags did not exhibit a discernible influence on Cp3GT kinetics, substrate preference, pH optima, or metal interactions, maintaining its specificity towards flavonols at the 3-OH position and favoring glucosylation of quercetin and kaempferol. Subsequent purification steps, including MonoQ anion exchange and size-exclusion chromatography, yielded Cp3GT with ≥95% homogeneity. In silico molecular models of Cp3GT and its truncated variants, Cp3GTΔ80 and Cp3GTΔ10, were constructed using D-I-TASSER and COFACTOR to assess binding interactions with quercetin and kaempferol. Results indicated minimal interference of c-myc/6x-his tags with the native Cp3GT structure. This study not only lays a foundation for impending crystallographic studies, aiming to solidify the understanding of Cp3GT\u27s stringent 3-O flavonol specificity, but also accentuates the potential of microbial expression platforms and plant metabolic engineering in producing beneficial compounds. To this end, a thorough review of four pivotal classes of plant secondary metabolites, flavonoids, alkaloids, betalains, and glucosinolates, was conducted. This will open avenues for further research and applications in biotechnological, medical, and agricultural domains
30th European Congress on Obesity (ECO 2023)
This is the abstract book of 30th European Congress on Obesity (ECO 2023
The effects of herbal extracts and compounds on the glucose metabolism in HepG2 cells
The aim of this study is to investigate the effects of herbal substances on glucose metabolism in HepG2 cellular models, this project's main objective was to evaluate and compare the metabolic activities of HepG2 cells following treatment with herbal compounds and botanical extracts like phloretin, ouabain, berberine, metformin, rebaudioside-A, and Stevia extracts, goldenseal extracts, goat's rue extracts, and Gymnema extracts.
In the screening tests, changes in glucose uptake in response to treatment with extracts and individual compounds were recorded. Extracts of goldenseal (Hydrastis candensis L.) and the alkaloid berberine induced remarkable glucose uptake, and consumption, compared with the other compounds and extracts. And demonstrated significant glucose uptake (p<0.05, p<0.01) and consumption activity (p<0.05, p<0.001) when compared to the biguanide drug metformin (p<0.01). As a result, goldenseal ethanolic extracts (10µL/mL) and berberine (10µM) were identified as the key candidates of the research to investigate glucose uptake using flowcytometry, Glucose transporter-1, estimation of glycogen content and glucose release, and seahorse metabolic analysis. In glucose uptake studies using flowcytometry, berberine augmented 3.4 times more glucose uptake, goldenseal stimulated 2 times, and metformin upsurges 1.8 times compared to the control (p<0.001). In the glucose transporter-1 expression assays, goldenseal, and berberine were augmented the expression 1.7 times and 1.4 times compared to the control (p<0.05).
Berberine was upregulated 2.4 times, metformin twice, and goldenseal twice in glycogen synthesis studies after long-term treatment (p<0.05). In glucose release assays, berberine, metformin, and goldenseal releasing 50%, 30%, and 23% less glucose compared to the control (p<0.05). The Seahorse XF analysis, which is more in line with the literature, shows that the three treatments increase the rate of lactate production (p<0.01) while also improving glucose metabolism. When compared to the pure compound alkaloid berberine, goldenseal extract was found to be less effective in improving glucose metabolism. Nonetheless, both appear promising for the development of new oral anti-diabetic medications
Evaluation of the toxicity of secondary metabolites in Solanum incanum L. to advance community knowledge
The effects of pests and the need to produce adequate food have influenced small-scale farmers in disadvantaged communities to adopt and utilise natural plant pesticides to improve harvests in many Southern African Development Communities. However, the phytochemistry associated with these indigenous plants’ pesticide activity still needs to be explored. The lack of evidence of scientific knowledge of the plant species has caused a lot of health issues among the users of indigenous plant pesticides. Solanum incanum is among the plants utilised to control cabbage aphids in Mkoba village, Zimbabwe. Solanum species are known for their steroidal compounds which comprise glycoalkaloids and saponins. This study evaluated the knowledge, opinions, and attitudes of the vegetable peasant farming community in Gweru regarding their use of the indigenous plant (S. incanum) as a pesticide. The study also reported the phytochemical profiling, structural characterisation of the isolated compounds, and biological and pesticidal activity evaluation of phytochemicals isolated from S. incanum. A descriptive survey was carried out to assess the knowledge, attitude, and practices of a conveniently sampled group of vegetable farmers in Mkoba village who use S. incanum as a pesticide. Forty-nine respondents comprised of 19 males and 30 females of ages ranging from 15 to above 60 years took part in the study by answering an open and closed-ended questionnaire. The survey revealed that parents and neighbours were instrumental in disseminating pesticidal information in the community. Brassica napus were the most grown.vegetable and vulnerable to cabbage aphids. Mixed opinions amongst the respondents varied regarding the health and environmental impact of S. incanum as a pesticide. Seventy-five percent (75%) of the respondents supported the use of S. incanum as a pesticide whilst 25% claimed that the use of S. incanum was the source of the health problems experienced in the community. The survey demonstrated that (45)91% of the farmers displayed poor practices regarding the disposal of empty pesticide containers and the use of personal protective clothing. The most prevalent symptoms in the community were skin rash, nausea, headache, and poor vision and these symptoms were common in the age group 30 to 60 years.Thesis (PhD) -- Faculty of Science, School of biomolecular and Chemical Sciences, 202
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