Unveiling the potential of medicinal herbs as the source for in vitro screening toward the inhibition of Nrf2.

Background: Drug resistance is one of the leading causes attributed to the failure of cancer treatment by chemotherapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating gene expression in cell defense against oxidative stress or hazardous factors. Taking advantage of this feature, Nrf2 also serves as the bodyguard for both normal and cancer cells. Many pieces of evidence have reported that inhibiting Nrf2 activity in cancer cells can reverse chemotherapy drug resistance. In addition, secondary metabolites from medicinal plants have been reported to inhibit Nrf2 activity in the in vitro study. This study aimed to preliminarily investigate fractions from medicinal herbs that inhibit Nrf2 activity in Huh7 liver cancer cells, thereby establishing a basis for subsequent isolation and extraction processes. Materials and methods: Sub-fractions from five medicinal plants have been evaluated the Nrf2 inhibitor activity on Huh7 cells through luciferase-reported genes assay. Thin-layer chromatography (TLC) was also performed to quantify the extracts' main phytochemistry components. Combining the half-maximal inhibitory concentration (IC50) and half-maximal cytotoxicity concentration (CC50) enables us to determine which extracts have the potential for further isolation steps. Results: Ten over 30 crude extracts and sub-fractions showed the inhibition of Nrf2 activity with the percentage ranging from 30 to 97 %. The methanol and n-hexane sub-fractions from Helicteres hirsuta Lour. leaves showed the strongest inhibition ability on Nrf2 activity with the IC50 = 20.98 ± 3.67 and 42.22 ± 2.10 µg/mL, respectively. The TLC results showed the presence of steroids and terpenoids in the promising sub-fractions. Conclusions: Combining the TLC results with the in vitro screening on Nrf2 activity screening of medicinal plants, the outcomes suggest the steroids and terpenoids in the methanol extract and hexane sub-fraction from Helicteres hirsuta Lour. leaves show promise towards inhibiting Nrf2 activity in liver cancer cell lines without toxicity in the normal cells.

Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.