Mechanism of polyphyllin Ⅰ targeting EGFR to affect proliferation and apoptosis of human breast cancer cells / 中国中药杂志

This study aims to investigate the molecular mechanism of polyphyllin Ⅰ(PPⅠ) inhibiting proliferation of human breast cancer cells. Human breast cancer BT474 and MDA-MB-436 cells were treated with different concentrations of PPⅠ, and then the effect of PPⅠ on cell proliferation was detected by MTT assay, trypan blue dye exclusion assay, real-time cell analysis, and clone forming assay, respectively. The apoptosis was detected by Annexin V-FITC/PI staining and then analyzed by flow cytometry. The change of mitochondrial membrane potential was detected by flow cytometry after fluorescent probe JC-1 staining. Western blot was used to detect protein expression and phosphorylation. Molecular docking was performed to detect the binding between PPⅠ and EGFR. The affinity between PPⅠ and EGFR was determined by drug affinity responsive target stability assay. The results indicated that PPⅠ inhibited the proliferation and colony formation of BT474 and MDA-MB-436 cells in a time-and concentration-dependent manner. The PPⅠ treatment group showed significantly increased apoptosis rate and significantly decreased mitochondrial membrane potential. PPⅠ down-regulated the expression of pro-caspase-3 protein, promoted the cleavage of PARP, and significantly reduced the phosphorylation levels of EGFR, Akt, and ERK. Molecular docking showed that PPⅠ bound to the extracellular domain of EGFR and formed hydrogen bond with Gln366 residue. Drug affinity responsive target stability assay confirmed that PPⅠ significantly prevented pronase from hydrolyzing EGFR, indicating that PPⅠ and EGFR have a direct binding effect. In conclusion, PPⅠ inhibited the proliferation and induced apoptosis of breast cancer cells by targeting EGFR to block its downstream signaling pathway. This study lays a foundation for the further development of PPⅠ-targeted drugs against breast cancer.

Paris saponin VII, a direct activator of AMPK, induces autophagy and exhibits therapeutic potential in non-small-cell lung cancer / 中国天然药物

Paris saponin VII (PSVII), a bioactive constituent extracted from Trillium tschonoskii Maxim., is cytotoxic to several cancer types. This study was designed to explore whether PSVII prevents non-small-cell lung cancer (NSCLC) proliferation and to investigate its molecular target. AMP-activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. In cultured human NSCLC cell lines, PSVII induces autophagy by activating AMPK and inhibiting mTOR signaling. Furthermore, PSVII-induced autophagy activation was reversed by the AMPK inhibitor compound C. Computational docking analysis showed that PSVII directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSVII and AMPK. In summary, PSVII acts as a direct AMPK activator to induce cell autophagy, which inhibits the growth of NSCLC cells. In the future, PSVII therapy should be applied to treat patients with NSCLC.

Research Progress in Distinguishing Methods of Simultaneous Multiple Primary Lung Cancer and Intrapulmonary Metastasis / 中国肺癌杂志

Multiple primary lung cancer (MPLC) refers to lung cancer in which two or more primary lesions occurred simultaneously or successively in different parts of the same patient's lungs. The diagnosis interval is 6 months. MPLC is divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC). sMPLC and intrapulmonary metastasis (IM) are different in treatment strategies and prognosis. However, there are many controversies about the distinction between the two in clinical practice. This article summarizes the current main methods of diagnosing MPLC, and focuses on the latest research progress in distinguishing MPLC from IM. It aims to provide a theoretical basis for accurate diagnosis and treatment of patients with multifocal lung cancer.
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Therapeutic Observation of Scalp Cluster Needling plus Acupuncture at Conception Vessel Points for Generalized Anxiety Disorder / 上海针灸杂志

Objective To observe the clinical efficacy of scalp cluster needling plus acupuncture at Conception Vessel points in treating generalized anxiety disorder.Method Sixty eligible subjects were divided into a treatment group and a control group by the random number table, 30 cases each. The treatment group was intervened by scalp cluster needling plus acupuncture at Conception Vessel points including Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12) and Xiawan (CV10); in the control group, Shenmen (HT7), Daling (PC7), Neiguan (PC6), Qimen (LR14), Xinshu (BL15), Hegu (LI4) and Taichong (LR3) were selected. The treatments were given once a day, 6 sessions followed by 1-day interval as a treatment course, for successive 8 courses in total. The Hamilton Anxiety Scale (HAMA) scores of the two groups were compared before and after the treatment and in the follow-up study; the clinical efficacies were also compared.Result The treatment protocols in the two groups were both effective in treating generalized anxiety disorder, while the markedly effective rate was significantly higher in the treatment group than in the control group (P<0.05). The HAMA scores after treatment and in the 1-month follow-up study were significantly different from the score before the treatment in both groups (P<0.01). There were significant differences in comparing the HAMA score between the two groups respectively after treatment and in the 1-month follow-up study (P<0.05). Conclusion Scalp cluster needling plus acupuncture at Conception Vessel points shows significant advantage in treating generalized anxiety disorder compared to the ordinary acupuncture method.

Therapeutic Observation of Scalp Cluster Needling plus Acupuncture at Conception Vessel Points for Generalized Anxiety Disorder / 上海针灸杂志

Objective To observe the clinical efficacy of scalp cluster needling plus acupuncture at Conception Vessel points in treating generalized anxiety disorder.Method Sixty eligible subjects were divided into a treatment group and a control group by the random number table, 30 cases each. The treatment group was intervened by scalp cluster needling plus acupuncture at Conception Vessel points including Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12) and Xiawan (CV10); in the control group, Shenmen (HT7), Daling (PC7), Neiguan (PC6), Qimen (LR14), Xinshu (BL15), Hegu (LI4) and Taichong (LR3) were selected. The treatments were given once a day, 6 sessions followed by 1-day interval as a treatment course, for successive 8 courses in total. The Hamilton Anxiety Scale (HAMA) scores of the two groups were compared before and after the treatment and in the follow-up study; the clinical efficacies were also compared.Result The treatment protocols in the two groups were both effective in treating generalized anxiety disorder, while the markedly effective rate was significantly higher in the treatment group than in the control group (P<0.05). The HAMA scores after treatment and in the 1-month follow-up study were significantly different from the score before the treatment in both groups (P<0.01). There were significant differences in comparing the HAMA score between the two groups respectively after treatment and in the 1-month follow-up study (P<0.05). Conclusion Scalp cluster needling plus acupuncture at Conception Vessel points shows significant advantage in treating generalized anxiety disorder compared to the ordinary acupuncture method.

Curative effects of sitagliptin in the treatment of type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease / 中国基层医药

Objective To evaluate the curative effects of sitagliptin in the treatment of type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease(NAFLD).Methods 200 type 2 diabetes mellitus patients with NAFLD were selected and randomly divided into the observation group and the control group,100 cases in each group.The observation group received sitagliptin treatment,while the control group was treated with metformin.Before and 3,6 months after treatment,the body weight,body mass index(BMI),liver function(AST,ALT,GGT),OGCT synchronous exsanguinate assay(fasting and 2 h after breakfast glucose,insulin),blood lipid(TC,TG)and glycosylated hemoglobin(HbAlc),and other biochemical indicators were monitored and compared,as well as 1HMRS scan images. Results In the two groups after treatment,ALT,GGT,AST,FPG and 2h PG all improved significantly(t≥2.35,P <0.05),but ALT,GGT,AST,FPG and 2h PG in the observation group all improved better than those in the control group(t≥4.99,all P <0.05).In the two groups after treatment,TC,TG,HbAlc,BMI,HOMA -IR all improved significantly(t≥5.63,all P <0.05),but those of the observation group improved more significantly(t≥3.90,all P <0.05 ).In the observation group after treatment,liver lipid content (IHCL)was (10.3 ±2.9 )%,which was significantly lower than (27.8 ±4.5)% before treatment(t =32.69,P <0.05).In the control group after treatment, IHCL was (18.4 ±3.5)%,which was significantly lower than (26.9 ±4.6)% before treatment(t =14.70,P <0.05),but in the observation group after treatment IHCL was significantly lower than that in the control group after treatment(t =17.82,P <0.05).Conclusion Sitagliptin can significantly improve the blood glucose,blood lipid, liver function,insulin resistance in type 2 diabetes mellitus patients with NAFLD,which has good clinical curative effects and is worthy of clinical promoting.