Hepatocellular carcinoma (HCC), the most common type of malignant tumor of the digestive system, is associated with high morbidity and mortality. The main treatment for HCC is surgical resection. Advanced disease, recurrence, and metastasis are the main factors affecting prognosis. Chemotherapy and radiotherapy are not sufficiently efficacious for the treatment of primary and metastatic HCC; therefore, optimizing targeted therapy is essential for improving outcomes. Forkhead box O (FOXO) proteins are widely expressed in cells and function to integrate a variety of growth factors, oxidative stress signals, and other stimulatory signals, thereby inducing the specific expression of downstream signal factors and regulation of the cell cycle, senescence, apoptosis, oxidative stress, HCC development, and chemotherapy sensitivity. Accordingly, FOXO proteins are considered multifunctional targets of cancer treatment. The current review discusses the roles of FOXO proteins, particularly FOXO1, FOXO3, FOXO4, and FOXO6, in HCC and establishes a theoretical basis for the potential targeted therapy of HCC.
BackgroundObservational studies about the association between serum total bilirubin and cholelithiasis are inconsistent. Hence, it is essential to reevaluate the association between serum total bilirubin and cholelithiasis and to verify whether such association is causal or not.MethodsWe selected single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure as instrumental variable and conducted a bidirectional two-sample Mendelian randomization (MR) study to explore the causal association between serum total bilirubin and cholelithiasis. We implemented the inverse-variance weighted approach as a primary analysis to combine the Wald ratio estimates. Four additional analyses, namely, MR-Egger regression, weighted median, weighted mode, and MR–pleiotropy residual sum and outlier (PRESSO), were utilized to investigate the causal association and the influence of potential pleiotropy.ResultsA total of 116 SNPs were selected as valid instrumental variables to estimate the causal association of serum total bilirubin on cholelithiasis, and causal association between genetically determined serum total bilirubin and cholelithiasis was demonstrated [beta = 0.10; 95% confident interval (CI), 0.07 to 0.14; p < 0.001]. Likewise, the other methods, namely, the weighted median (beta = 0.12; 95% CI, 0.08 to 0.15; p < 0.001), MR-Egger (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), weighted mode (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), and MR-PRESSO approaches, further confirmed that this result (p = 0.054) indicates similar results. In addition, seven SNPs were selected as instrumental variable to estimate causal association of cholelithiasis on serum total bilirubin, and the result supported the causal effect of cholelithiasis to serum total bilirubin (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001). At the same time, the other methods, namely, the weighted median (beta = 0.10; 95% CI, 0.06 to 0.13; p < 0.001), MR-Egger (beta = 0.12; 95% CI, 0.07 to 0.18; p = 0.007), weighted mode (beta = 0.09; 95% CI, 0.03 to 0.14, p = 0.019), and MR-PRESSO methods, further confirmed this result (p < 0.001).ConclusionOur MR study revealed that the serum total bilirubin was causally associated with the risk of cholelithiasis, and the genetic predisposition to cholelithiasis was causally associated with the increased serum total bilirubin levels.
With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.
Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.