Effects of Scutellaria strigillosa Hemsl. extract on HepG2 cell proliferation and apoptosis through binding to aspartate ß-hydroxylase.

This study aims to examine the impacts of Scutellaria strigillosa Hemsl. (SSH) on the proliferation, apoptosis of human hepatoma cell HepG2 and screen the bioactive components. We found that SSH extract inhibited HepG2 proliferation, arrested cell division prior to S phase. Additionally, SSH extract exposure induced apoptosis, and increased the proportions of late apoptotic cells. Specifically, we focus on the inhibitory effect of SSH extract on aspartate ß-hydroxylase, a key therapeutic target of hepatocellular carcinoma closely related with the proliferation and apoptosis of HepG2. We found SSH extract with notable inhibitory activity against aspartate ß-hydroxylase, elucidated the main bioactive constituents by HPLC-Q-TOF/MS and Molecular docking analysis. In conclusion, these results provided the antiproliferative and proapoptotic effects of SSH on HepG2 cell, elucidated the main bioactive constituents based on aspartate ß-hydroxylase inhibition. These data revealed the potential value of SSH and its bioactive components for the prevention and treatment of liver cancer for the first time.

Public Psychosocial and Behavioral Responses in the First Wave of COVID-19 Pandemic: A Large Survey in China.

Background: The COVID-19 has grown into a global pandemic. This study investigated the public psychosocial and behavioral responses through different time periods of the pandemic, and assessed whether these changes are different in age, gender, and region. Methods: A three-phase survey was conducted through the DaDui Social Q&A Software for COVID-19. A total of 13,214 effective responses of COVID-19 were collected. Statistical analysis was performed based on their basic information and psychosocial responses. Results: The degree of attention, understanding, and cooperation with preventive and control measures of the disease increased and then decreased. The panic level gradually increased with the epidemic process. The degree of satisfaction with management measures and of confidence in defeating COVID-19 increased throughout the survey. Compared with residents in other areas, respondents from the COVID-19 epicenter (Wuhan) reported a higher degree of self-protection during the outbreak and a significantly lower degree of satisfaction with respect to government prevention and control measures during all phases. Shortages of medical supplies and low testing capacity were reported as the biggest shortcoming in the prevention and control strategies during COVID-19, and an abundance of disorderly and inaccurate information from different sources was the primary cause of panic. Conclusions and Relevance: Major public health events elicit psychosocial and behavioral changes that reflect the different phases of the biologic curve. Sufficient medical supplies and improved organization and accurate information during epidemics may reduce panic and improve compliance with requested changes in behavior. We need to recognize this natural phenomenon and our public policy preparedness should attempt to move the social/psychological curve to the left in order to minimize and flatten the biologic curve.

Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field.

INTRODUCTION: Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment. METHODS: The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. RESULTS: The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy. CONCLUSIONS: Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.

Ulixertinib (BVD-523) antagonizes ABCB1- and ABCG2-mediated chemotherapeutic drug resistance.

Ulixertinib (BVD-523) is a highly potent, selective, and reversible ERK1/2 inhibitor and is currently in clinical development for the treatment of advanced solid tumors. In this study, we investigated whether ulixertinib could antagonize multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters. The results showed that ulixertinib, at non-toxic concentrations, significantly reversed ATP-binding cassette subfamily B member 1 (ABCB1)- and ATP-binding cassette subfamily G member 2 (ABCG2)-mediated MDR. In ABCB1-overexpressing cells, ulixertinib antagonized MDR by attenuating the efflux function of ABCB1. Similarly, in ABCG2-overexpressing cells, ulixertinib inhibited the efflux activity of ABCG2 and reversed resistance to substrate anticancer drugs. The reversal effects of ulixertinib were not related to the down-regulation or change of subcellular localization of ABCB1 or ABCG2. Mechanistic investigations revealed that ulixertinib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner, and the in silico docking study predicted that ulixertinib could interact with the substrate-binding sites of both ABCB1 and ABCG2. Our finding provides a clue into a novel treatment strategy: a combination of ulixertinib with anticancer drugs to attenuate MDR mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters.