Abstract:

Green tea catechins have been studied for their health benefits for many decades. These beneficial effects include anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory and neuroprotective properties. The anti-cancer benefits have been reported to be related to up and down-regulation of microRNAs (miR), which are small, non-coding RNA molecules involved in cell proliferation, differentiation, apoptosis, and angiogenesis. However, studies have shown that these catechins, including the most abundant, (-)-epigallocatechin gallate (EGCG), are poorly absorbed in the intestinal tract. It is known that the microbiota plays a crucial role in catechin metabolization, degrading and producing ring-fission metabolites, increasing their bioavailability. This research aims to investigate the effects of the major metabolite of EGCG, 5-(3′,5′-dihydroxyphenyl)-γ-valerolactone (M5), on microRNA expression in colorectal cancer HCT116 cells. A commercial sample of green tea extract was incubated with bacterial strains Eggerthela lenta (JCM 9979) and Flavonifractor plautii (ATCC 29863), to obtain M5. M5 was purified, and NMR and optical rotation analysis confirmed its structure. HCT116 cells were exposed to 25, 50, and 100 μM of EGCG and M5 for 24 h. Analysis for miR-494-3p and 1226-3p by RT-qPCR suggests that M5 has higher activities on miR up and down-regulation when compared to EGCG. Using prediction tools such as TargetScan and miRDB, microRNA targets were selected and analyzed by RT-qPCR. Multiple targets showed down-regulation, including VASH1 (vasohibin 1) and DUSP4 (dual specificity phosphatase 4), biomarkers related to angiogenesis and cancer progression, respectively. Further experiments are ongoing to better understand the anti-cancer activity of M5.

Abstract:
Quinoxaline is a heterocyclic compound with a two-membered ring structure that undergoes redox cycling to produce toxic free radicals. It has antiviral, antibacterial, antifungal, and antitumor activities. However, the biological functions that are involved in mounting a response against the toxic effects of quinoxaline have not been investigated.
Results: Herein, we performed a genome-wide screen using the yeast haploid mutant collection and reported the identification of 12 mutants that displayed varying sensitivity towards quinoxaline. The quinoxaline-sensitive mutants were deleted for genes that encode cell cycle function, as well as genes that belong to other physiological pathways such as the vacuolar detoxification process. Three of the highly sensitive gene-deletion mutants lack the DDC1, DUN1, and MFT1 genes. While Ddc1 and Dun1 are known to perform roles in the cell cycle arrest pathway, the role of Mft1 remains unclear. We show that the mft1Δ mutant is as sensitive to quinoxaline as the ddc1Δ mutant. However, the double mutant ddc1Δ mft1Δ lacking
the DDC1 and MFT1 genes, is extremely sensitive to quinoxaline. We further show that the mft1Δ mutant is unable to arrest in the G2/M phase in response to the drug. Conclusion: This is the first demonstration that quinoxaline exerts its toxic effect likely by inducing oxidative DNA damage causing cell cycle arrest. We suggest that clinical applications of quinoxaline and its derivatives should entail targeting cancer cells with defective cell cycle arrest.

Abstract:

The threat posed by the blood-borne pathogens is disproportionately distributed in different healthcare facilities in Cameroon. Thus, there is a need for continuous surveillance of TTIs in the country. This study aimed to assess the screening procedure for blood transfusion and determine the trend in immunological markers of TTIs among blood donors at the Mamfe District Hospital (MDH). A prospective descriptive and cross-sectional study was conducted at Mamfe District Hospital in 2022. A total of 165 blood donors were recruited and screened using both Rapid diagnostic tests and indirect ELISA for the detection of TTIs. Data generated was entered into an Excel spreadsheet and analysed using the statistical software R, version 4.2.0. Student t-test was used to compare both diagnostic techniques, and was considered significant when p < 0.05. The majority (75.20%) of the donors were of the O-positive blood type, repeat donors (69.10%) and were mainly family replacement and paid donors as against the voluntary blood donors (39.40% and 37.00% vs. 23.60% respectively). overall TTIs prevalence was 18.78% (31/165), with HBsAg being the most predominant marker (12.12%) followed by Treponema pallidum, HCV and HIV antibodies at 4.85% 1.21% and 0.60% respectively. Except for the HBV, The prevalence of TTIs was higher when using a single RDT than the ELISA test, and the difference was significant (p<0.05). Blood borne pathogens remain a major menace to safe blood transfusion practice in MDH. Therefore, the donor screening protocol in MDH should systematically incorporate a confirmation diagnostic test such as ELISA.

Abstarct:

Immortal time bias (ITB) is common in cohort studies and biases the association estimates between the treated and untreated individuals. We used data from an Italian study on COVID-19 vaccine effectiveness, with a large cohort, long follow-up, and adjustment for confounding factors, but affected by ITB. We verified the real impact of the vaccination campaign, comparing the risk of all-cause death between the vaccinated and the unvaccinated population.

We aligned all subjects on a single index date and considered the “all-cause deaths” outcome to compare the survival distributions of the unvaccinated group versus various vaccination statuses. The all-cause-death hazard ratios (HRs) in univariate analysis for vaccinated people with 1, 2, and 3/4 doses versus unvaccinated people were 0.88, 1.23, and 1.21, respectively. The multivariate values were 2.40, 1.98, and 0.99. Possible explanations of this trend of the HRs as vaccinations increase could be: a harvesting effect; a calendar-time bias, accounting for seasonality and pandemic waves; a case-counting window bias; a healthy-vaccinee bias; or some combination of these factors. With 2 and even with 3/4 doses, the calculated Restricted Mean Survival Time and Restricted Mean Time Lost showed a small but significant downside for the vaccinated populations.

The study results should lead to rethink political choices about pandemic management, supporting greater caution in the future.