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Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.

Herui Li,&ast; Yiming Ma,&ast; Zihang Zeng, Lijuan Luo, Tiao Li, Huihui Zeng, Yan Chen Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Huihui Zeng, Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People’s Republic of China, Email chenyan99727@csu.edu.cn; bonemarrow@csu.edu.cnBackground: Surgical and medical treatments are applied to pulmonary cryptococcosis (PC) in the real world, while the prognosis of different therapies is uncertain. This study investigated diagnosis, real-world therapy, follow-up outcomes, and prognosis factors, aiming to deepen our understanding of PC.Methods: Patients pathologically diagnosed with PC were retrospectively reviewed and followed up. Further comparisons and subgroup analyses were conducted in surgical and nonsurgical treatment individuals. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with treatment failure.Results: One hundred and sixty-three patients were included in this study, of whom 92 underwent surgical removal of VATS or open lung surgery (68 of them received postoperative antifungal treatment) and 71 got antifungal drugs only. Compared with nonsurgical patients, surgical patients were more immunocompetent (73 [79.3%] cases vs 33 [46.5%]), showed milder symptoms and more limited pulmonary lesions. Although they had instant treatment response owing to lesions resection, there is no significant advantage in the rate of treatment failure. Multivariable regression showed independent predictive factors associated with treatment failure were polymorphonuclear (PMN)> 6.30&ast;109/L, albumin (Alb) < 40g/L and antifungal dosage < 400mg/d. Further analysis among patients with different immune statuses or symptoms demonstrated that sufficient antifungal dosage could reduce the rate of treatment failure.Conclusion: PC showed variable and nonspecific clinical features. PC patients with limited nodules/masses and mild symptoms often led to misdiagnosis and unnecessary lung resections. The potential risk factors including higher PMN and hypoalbuminemia could help clinicians to identify PC patients with poor treatment efficiency at an early stage. To note, sufficient antifungal dosage may improve the treatment outcomes.Keywords: pulmonary cryptococcosis, diagnosis, antifungal treatment, clinical features, surgery