Maimendong and Qianjinweijing Tang combined with cisplatin suppressed lung cancer through targeting lncRNA-p21.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY: To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS: A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS: Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS: This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.

[A successfully treated case of colchicine poisoning with lethal dose].

At present, there is no specific antidote for colchicine intoxication, and 0.8 mg/kg is its lethal dose. The prognosis of colchicine intoxication patients is closely related to the dosage, but the individual difference is very great. A 38-year-old man with colchicine poisoning was admitted to the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, who had ingested 80 mg colchicine tablets (1.19 mg/kg) orally for 4 hours. He was immediately put on gastric lavage, enema, and catharsis. Continuous blood purification was performed for 34 hours and 22 minutes, with a combination of hemoperfusion (HP) and continuous veno-venous hemofiltration dialysis (CVVHDF). He also received a large dose of the glucocorticoid with 80 mg of methylprednisolone injected intravenously every 8 hours and organ function support. The patient was hospitalized for 2 weeks and discharged with improvement. The successful treatment of this case was reported for reference.

A new methylene bisflavan-3-ol from the branches and leaves of Potentilla fruticosa.

Dasiphora fruticosa L. (Rosaceae), also known as Potentilla fruticosa L. (syn.), is a hardy deciduous shrub widely distributed in the north temperate regions of the world. Three methylene bisflavan-3-ols (1-3), together with a procyanidin dimer, (-)-afzelechin-(4α→8)-(-)-afzelechin (4) were isolated for the first time from the branches and leaves of the titled plant, in addition to 11 known compounds (5-15). Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures. Methylene 6,8-bis(7-O-glucosyl) catechin (1) was determined to be a new dimeric flavan-3-ol glycoside through a methylene linkage between C-8 and C-8 of two units. At a concentration of 128 µg/mL, the known compounds 9 - 13 exhibited antibacterial activities on Escherichia coli, Staphylococcus aureus subsp. aureus, Salmonella enterica subsp. enterica, and Pseudomonas aeruginosa. Compound 12 also showed certain glucose uptake stimulating activity.

[Effect of electroacupuncture on renal fibrosis in spontaneously hypertension rats and its related mechanisms].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. METHODS: Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. RESULTS: The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. CONCLUSION: EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.

A GPR17-cAMP-Lactate Signaling Axis in Oligodendrocytes Regulates Whole-Body Metabolism.

The CNS plays a pivotal role in energy homeostasis, but whether oligodendrocytes are involved has been largely unexplored. Here, we show that signaling through GPR17, a G-protein-coupled receptor predominantly expressed in the oligodendrocyte lineage, regulates food intake by modulating hypothalamic neuronal activities. GPR17-null mice and mice with an oligodendrocyte-specific knockout of GPR17 have lean phenotypes on a high-fat diet, suggesting that GPR17 regulates body weight by way of oligodendrocytes. Downregulation of GPR17 results in activation of cAMP-protein kinase A (PKA) signaling in oligodendrocytes and upregulated expression of pyruvate dehydrogenase kinase 1 (PDK1), which promotes lactate production. Elevation of lactate activates AKT and STAT3 signaling in the hypothalamic neurons, leading to increased expression of Pomc and suppression of Agrp. Our findings uncover a critical role of oligodendrocytes in metabolic homeostasis, where GPR17 modulates the production of lactate, which, in turn, acts as a metabolic signal to regulate neuronal activity.

Moxibustion Alleviates Injury in a Rat Focal Segmental Glomerulosclerosis Model.

OBJECTIVES: To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. METHODS: A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored. RESULTS: Urinary protein, serum creatinine, urea nitrogen, and serum uric acid were significantly reduced after 12-week intervention with losartan, Shenshu, or Geshu moxibustion. Renal α-SMA, FN, and TGF-ß were also decreased, while podocin and nephrin protein and mRNA were increased. The pathological damage in renal tissue was obviously alleviated by all three treatments, which suggests that moxibustion may have similar efficacy to losartan in the treatment of FSGS. CONCLUSION: Moxibustion alleviates podocyte injury and inhibits renal interstitial fibrosis in the FSGS rat model, thereby minimizing the progression of glomerular sclerosis and improving renal function.

[Effect of Mild Moxibustion with Different Terms at Different Acupoints on Renal Functions and Renal Pathological Changes in Focal Segmental Glomerulosclerosis Rats].

OBJECTIVE: To observe changes of urinary microprotein, and serum creatinine, urea nitrogen and uric acid levels in focal segmental glomerulosclerosis (FSGS) rats treated by mild moxibustion, so as to explore the mechanism of moxibustion underlying improvement of FSGS. METHODS: SD rats were randomized into normal control (normal), sham operation (sham), model, medication (Losartan), moxibustion-Shenshu (BL 23) and moxibustion-Geshu (BL 17) groups. The latter two moxibustion groups were further divided into 10 min, 20 min and 30 min subgroups (n=6 in each group/subgroups). The FSGS model was established by unilateral nephrectomy combined with injection of Losartan into the tail vein twice. Mild moxibustion was applied to bilateral BL 17 and BL 23 for 10, 20 and 30 min, respectively, once every other day, for 12 weeks. The contents of urinary microglobulin α 1, micro-albumin, transferring and IgG were assayed using enzyme linked immunosorbent assay (ELISA), and serum creatinine, urea nitrogen and uric acid contents (indexes of renal function) determined using an automatic biochemical analyzer. The pathological changes of the kidney tissue was observed by using a microscope after periodic acid schiff (PAS) staining. RESULTS: No significant differences were found between the normal control and sham groups in the levels of all the urinary and serum indexes (P>0.05) and pathological changes of the renal tissues. Compared with the normal control group, the contents of urinary microglobulin α 1, micro-albumin, transferrin and IgG, and serum creatinine, urea nitrogen and uric acid were significantly increased in the model group (P<0.01). Following medication and moxibustion, the contents of the aforementioned 7 indexes in the Losartan group, and urinary microglobulin α 1, micro-albumin, transferrin and IgG, and serum creatinine levels in the moxibustion BL 23-20 min and 30 min groups, and the micro-albumin and transferrin contents in the BL-17 10 min group and IgG level in the BL-23 10 min group, the serum creatinine and urea nitrogen levels at the 3 time-points of both moxibustion BL 23 and BL 17 groups, and serum uric acid in the moxibustion BL 23 30 min, and BL17 20 and 30 min groups were all considerably down-regulated (P<0.05, P<0.01). The therapeutic effects of moxibustion 30 min were notably better than moxibustion 10 min in reducing urinary microglobulin α 1, micro-albumin, transferring and IgG levels (P<0.05, P<0.01). Results of PAS staining showed that the injury of the renal tissue as the endothelial and mesangial cellular proliferation, collagen proteinosis, interstitial fibrosis, etc were relatively milder in the Losartan and moxibustion 20 and 30 min groups. CONCLUSIONS: Mild moxibustion may reduce proteinuria, and improve the kidney function and pathological changes in FSGS rats, and longer duration of moxibustion is better in achieving therapeutic effect.