Studies on chronic myeloid leukemia (CML) have served as a paradigm for cancer research and therapy. These studies involve the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It becomes clear that leukemia stem cells (LSCs) in CML which are resistant to TKIs, and eradication of LSCs appears to be extremely difficult. Therefore, one of the major issues in current CML biology is to understand the biology of LSCs and to investigate why LSCs are insensitive to TKI monotherapy for developing curative therapeutic strategies. Studies from our group and others have revealed that CML LSCs form a hierarchy similar to that seen in normal hematopoiesis, in which a rare stem cell population with limitless self-renewal potential gives rise to progenies that lack such potential. LSCs also possess biological features that are different from those of normal hematopoietic stem cells (HSCs) and are critical for their malignant characteristics. In this review, we summarize the latest progress in CML field, and attempt to understand the molecular mechanisms of survival regulation of LSCs.
Animals ; DNA-Binding Proteins ; genetics ; metabolism ; Fusion Proteins, bcr-abl ; antagonists & inhibitors ; metabolism ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; metabolism ; pathology ; Lipid Metabolism ; Neoplastic Stem Cells ; drug effects ; metabolism ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-6 ; src-Family Kinases ; metabolism

Objective:To explore the efficacy and safety of open cardiac operation and interventional therapy in pregnant patients and describe the feto-neonatal and maternal outcomes.Methods:A retrospective study of 39 cases of women undergoing open cardiac operation or interventional therapy during pregnancy was conducted in Guangdong Provincial People′s Hospital from Jan. 2014 to Oct. 2019.Results:The age of 39 pregnant women with gestational heart disease was (30±6) years old (21-43 years old). Among them, 37 cases were single and 2 cases were twin pregnancy. Modified World Health Organization (mWHO) pregnancy risk classification were all level Ⅳ. There were 22 women receiving cardiac operation under cardiopulmonary bypass during pregnancy, 14 patients undergoing percutaneous balloon mitral valvuloplasty, 2 patients accepting percutaneous balloon pulmonary valvuloplasty, and 1 case receiving atrial septal defect occluder with ultrasound guidance. Three were no maternal deaths during and after the operation. One patient had an inevitable abortion. Four fetuses died in the uterine after open cardiac surgery. There patients chose termination of the pregnancy after cardiac operation. There were 31 live birth, in which 7 cases were preterm live birth and 24 patients were term live birth. The total number of newborns were 33. Two fetuses suffered neonatal intracranial hemorrhage and died after birth. Thirty-one fetuses were alive and born without any abnormity.Conclusion:For pregnant women with high risk of cardiovascular disease and classified as mWHO pregnancy risk level Ⅳ, cardiopulmonary bypass and interventional therapy during pregnancy could be used as an alternative for better materal and fetal outcomes.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/β-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.