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Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

Isodon rubescens has been used as a traditional green tea for more than 1000 years and many medicinal functions of I. rubescens are also very useful, such as its well-known antitumor and antibacterial activities. Oridonin, a bioactive ent-kaurane diterpenoid, is the major ingredient of this medicinal tea. Herein, 22 novel oridonin derivatives were designed and synthesized. The antibacterial activity was evaluated for the first time. Compound 12 was the most promising one with MIC of 2.0 μg/mL against B. subtilis, which was nearly 3-fold stronger than positive control chloromycetin. The antiproliferative property was also assayed and compound 19 showed stronger activity than taxol. The apoptosis-inducing ability, cell cycle arrest effect at S phase and influence of mitochondrial membrane potential by 19 in CaEs-17 cancer cells were first disclosed. Based on the above results, the cell apoptosis induced by compound 19 in CaEs-17 cells was most probably involved in the intrinsic apoptotic pathway.

Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4 , was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499- SOX6 / PDCD4 -BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

The liver stands out as one of the most frequent sites for distant metastasis in breast cancer cases. However, effective risk stratification tools for patients with breast cancer liver metastases (BCLM) are still lacking. We identified BCLM patients from the SEER database spanning from 2010 to 2016. After meticulously filtering out cases with incomplete data, a total of 3179 patients were enrolled and randomly divided into training and validation cohorts at a ratio of 2:1. Leveraging comprehensive patient data, we constructed a nomogram through rigorous evaluation of a Cox regression model. Validation of the nomogram was conducted using a range of statistical measures, including the concordance index (C-index), calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA). Both univariable and multivariable analyses revealed significant associations between OS and CSS in BCLM patients and 14 variables, including age, race, and tumor stage, among others. Utilizing these pertinent variables, we formulated nomograms for OS and CSS prediction. Subsequent validation involved rigorous assessment using time-dependent ROC curves, decision curve analysis, C-index evaluations, and calibration curves. Our web-based dynamic nomogram represents a valuable tool for efficiently analyzing the clinical profiles of BCLM patients, thereby aiding in informed clinical decision-making processes.