The impact of Lacticaseibacillus paracasei GMNL-143 toothpaste on gingivitis and oral microbiota in adults: a randomized, double-blind, crossover, placebo-controlled trial.

BACKGROUND: This study examines the oral health benefits of heat-killed Lacticaseibacillus paracasei GMNL-143, particularly its potential in oral microbiota alterations and gingivitis improvement. METHODS: We assessed GMNL-143's in vitro interactions with oral pathogens and its ability to prevent pathogen adherence to gingival cells. A randomized, double-blind, crossover clinical trial was performed on gingivitis patients using GMNL-143 toothpaste or placebo for four weeks, followed by a crossover after a washout. RESULTS: GMNL-143 showed coaggregation with oral pathogens in vitro, linked to its surface layer protein. In patients, GMNL-143 toothpaste lowered the gingival index and reduced Streptococcus mutans in crevicular fluid. A positive relationship was found between Aggregatibacter actinomycetemcomitans and gingival index changes, and a negative one between Campylobacter and gingival index changes in plaque. CONCLUSION: GMNL-143 toothpaste may shift oral bacterial composition towards a healthier state, suggesting its potential in managing mild to moderate gingivitis. TRIAL REGISTRATION: ID NCT04190485 ( https://clinicaltrials.gov/ ); 09/12/2019, retrospective registration.

Predicting Agents That Can Overcome 5-FU Resistance in Colorectal Cancers via Pharmacogenomic Analysis.

5-Fluorouracil (5-FU) is one of several chemotherapeutic agents in clinical use as a standard of care to treat colorectal cancers (CRCs). As an antimetabolite, 5-FU inhibits thymidylate synthase to disrupt the synthesis and repair of DNA and RNA. However, only a small proportion of patients benefit from 5-FU treatment due to the development of drug resistance. This study applied pharmacogenomic analysis using two public resources, the Genomics of Drug Sensitivity in Cancer (GDSC) and the Connectivity Map, to predict agents overcoming 5-FU resistance in CRC cells based on their genetic background or gene expression profile. Based on the genetic status of adenomatous polyposis coli (APC), the most frequent mutated gene found in CRC, we found that combining a MEK inhibitor with 5-FU exhibited synergism effects on CRC cells with APC truncations. While considering the gene expression in 5-FU resistant cells, we demonstrated that targeting ROCK is a potential avenue to restore 5-FU response to resistant cells with wild-type APC background. Our results reveal MEK signaling plays a pivotal role in loss-of-function, APC-mediated 5-FU resistance, and ROCK activation serves as a signature in APC-independent 5-FU resistance. Through the use of these available database resources, we highlight possible approaches to predict potential drugs for combinatorial therapy for patients developing resistance to 5-FU treatment.

Correction to "Melissa officinalis Extract Induces Apoptosis and Inhibits Migration in Human Colorectal Cancer Cells".

[This corrects the article DOI: 10.1021/acsomega.0c04489.].

Melissa officinalis Extract Induces Apoptosis and Inhibits Migration in Human Colorectal Cancer Cells.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Lifestyle-related factors, such as diet, are associated with the development of CRC. Cumulating evidence indicates noticeable chemopreventive effects of phytochemicals on CRC, suggesting that drinking herbal tea potentially reduces the risk of distal colon cancer via its antiproliferative and anti-angiogenic activities. We examine the antitumor effects of nine components frequently found in herbal tea and uncover the underlying molecular mechanism. Among them, the hot water extract of Melissa officinalis (MO) exhibited the highest anticancer activity on CRC cells. We revealed that MO reduced cell proliferation, induced cell cycle arrest at the G2/M phase, triggered caspase-dependent apoptotic cell death, and inhibited cell migration ability by modulating the epithelial-mesenchymal transition in HCT116 CRC cells. To examine the metabolite composition in the MO hot water extract, we applied mass spectrometry-based analysis and identified 67 compounds. Among them, the phenolic compounds, including lignans, phenylpropanoids, and polyketides, are widely found in natural products and possess various bioactivities such as anti-inflammatory, antioxidation, and anticancer effects. The results indicate that herbal tea consumption benefits CRC prevention and management.