Cordycepin Inhibits the Growth of Hepatocellular Carcinoma by Regulating the Pathway of Aerobic Glycolysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with a high incidence and mortality rate. Glucose metabolism reprogramming is a major characteristic of tumor cells. Increasing evidence indicates that aerobic glycolysis is associated with tumor growth and insensitivity to chemotherapy. Cordycepin inhibits the growth of HCC cells, but the mechanism is yet to be elucidated. Herein, in vitro and in vivo methods were utilized to investigate the cordycepin-inhibited growth of HCC by regulating the metabolic pathway of aerobic glycolysis. In vitro analyses using colony formation and flow cytometry revealed that cordycepin inhibits HCC cells' proliferation and promotes apoptosis. In addition, cordycepin reduced the production of lactic acid and pyruvate, reduced the uptake of glucose, and decreased the extracellular acidification in HCC cells. Specifically, cordycepin inhibited the expression of HK2, LDHA, and PKM2 in aerobic glycolysis via the AMPK-Akt pathway. Taken together, these findings revealed that cordycepin reduces the tumor energy supply and decreases lactic acid production, thereby inhibiting the growth of HCC cells by regulating the metabolic pathway of aerobic glycolysis. These findings might provide novel insights into the mechanisms underlying cordycepin-mediated inhibition of tumor growth as well as a new treatment for HCC.

Electroacupuncture improves cognitive deficits and insulin resistance in an OLETF rat model of Al/D-gal induced aging model via the PI3K/Akt signaling pathway.

To investigate the effect of electroacupuncture (EA) on cognitive function and insulin resistance (IR) in an Al/D-gal-induced aging model for Alzheimer's disease (AD) using Ostuka Long-Evans Tokushima Fatty (OLETF) rats. The Al/D-gal-OLETF rats for AD were randomly divided into the EA and non-EA groups. Cognitive function was assessed using the Morris water maze (MWM). The morphology of the hippocampal neurons was observed using hematoxylin & eosin (H&E) staining. Aß and total Tau in the hippocampus and cerebrospinal fluid (CSF) were detected using western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FPG) was determined using the glucose oxidase method. Plasma fasting insulin (FINS), serum C-peptide (C-P), and CSF insulin were detected using ELISA. The expression of the genes and proteins in the PI3K signaling pathway was detected using quantitative real-time PCR and WB. After EA intervention, the hippocampal Aß and total Tau protein levels, body weight, FPG, FINS, and C-P were significantly decreased. The MWM showed that the percentage of time in the target quadrant of the EA group was elevated in the probe test. The protein levels of p-IRS1, p-IRS2, IDE, and p-GSK3ß were significantly increased, while p-PI3K-p85α and p-Akt were decreased. In conclusion, EA improves cognitive function and insulin resistance in rat models of AD. The PI3K/Akt signaling pathway is involved in those changes.

Flower-like gold nanoparticles-based immunochromatographic test strip for rapid simultaneous detection of fumonisin B1 and deoxynivalenol in Chinese traditional medicine.

A flower-like gold nanoparticles (FGN)-based immunochromatographic test strip (ICS) was developed and used for the first time for the rapid simultaneous detection of fumonisin B1 (FB1) and deoxynivalenol (DON) in Chinese traditional medicine. Several experimental conditions affecting the sensitivity of ICS have been investigated, including the type of FGN, the preparation conditions of FGN-monoclonal antibody (MAb) conjugates, and the process parameters of ICS. Under the optimal experimental conditions, the visual limit of detection was 5.0 ng/mL (corresponding to 50 µg/kg in Chinese traditional medicine samples) for both FB1 and DON, and detection can be completed within 5 min. In addition, the natural samples were analyzed using high-performance liquid chromatography (HPLC) or enzyme-linked immunosorbent assay (ELISA), and the results of these methods showed good correlation with those obtained using ICS. The procedure using FGN-based simultaneous ICS was sensitive, rapid, and convenient for on-site detection of a large number of samples.

Comparative efficacy and safety of NSAIDs-controlled acupuncture in the treatment of patients with primary dysmenorrhoea: a Bayesian network meta-analysis.

BACKGROUND: Acupuncture and non-steroidal anti-inflammatory drugs (NSAIDs) are used frequently to treat primary dysmenorrhoea. However, it is unclear whether this treatment greatly reduces the risk of primary dysmenorrhoea. METHODS: Eight databases were searched up to January 2018. Pair-wise and network meta-analyses were conducted to synthesize data from eligible studies. RESULTS: Seventeen randomized controlled trials were included. The following acupuncture types showed more efficacy than NSAIDs in reducing primary dysmenorrhoea risk: traditional acupuncture (odds ratio [OR] = 6.70, 95% confidence interval [CI] 2.60-20.0), eye acupuncture (OR = 3.50, 95% CI 1.40-8.90), wrist-ankle acupuncture (OR = 6.00, 95% CI 1.30-32.0), superficial acupuncture (OR= 5.10, 95% CI 1.20-26.0), moxibustion (OR = 7.70, 95% CI 2.90-25.0), electroacupuncture (OR = 23.0, 95% CI 4.80-130), ear acupuncture (OR = 13.0, 95% CI 2.80-100) and abdominal acupuncture (OR = 5.30, 95% CI 2.10-16.0). Surface under the cumulative ranking curve values were traditional acupuncture (53.0%), eye acupuncture (22.0%), wrist-ankle acupuncture (81.5%), superficial acupuncture (50.0%), moxibustion (57.8%), electroacupuncture (99.9%), ear acupuncture (41.6%) and abdominal acupuncture (44.1%). CONCLUSION: Acupuncture is more efficacious than NSAIDs in reducing primary dysmenorrhoea risk. Acupuncture, particularly electroacupuncture, can decrease the risk of primary dysmenorrhoea.

Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats.

To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD) rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6), Zusanli (ST36), and Sanyinjiao (SP6); in contrast, acupuncture to Shenshu (BL23) was administered perpendicularly. For Neiguan (PC6) and Zusanli (ST36), needles were connected to an electroacupuncture (EA) apparatus. Fasting blood glucose (FPG) was measured by glucose oxidase method. Plasma fasting insulin (FINS) and serum C peptide (C-P) were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR), which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

Ubisol-Q10 Prevents Glutamate-Induced Cell Death by Blocking Mitochondrial Fragmentation and Permeability Transition Pore Opening.

Mitochondrial dysfunction and oxidative stress are the major events that lead to the formation of mitochondrial permeability transition pore (mPTP) during glutamate-induced cytotoxicity and cell death. Coenzyme Q10 (CoQ10) has widely been used for the treatment of mitochondrial disorders and neurodegenerative diseases. Comparing to traditional lipid-soluble CoQ10, water soluble CoQ10 (Ubisol-Q10) has high intracellular and intra-mitochondrial distribution. The aims of the present study are to determine the neuroprotective effects of Ubisol-Q10 on glutamate-induced cell death and to explore its functional mechanisms. HT22 neuronal cells were exposed to glutamate. Cell viability was measured and mitochondrial fragmentation was assessed by mitochondrial imaging. The mPTP opening was determined by mitochondrial membrane potential and calcium retention capacity. The results revealed that the anti-glutamate toxicity effects of Ubisol-Q10 was associated with its ability to block mitochondrial fragmentation, to maintain calcium retention capacity and mitochondrial membrane potential, and to prevent mPTP formation, AIF release, and DNA fragmentation. We concluded that Ubisol-Q10 protects cells from glutamate toxicity by preserving the integrity of mitochondrial structure and function. Therefore, adequate CoQ10 supplementation may be beneficial in preventing cerebral stroke and other disorders that involve mitochondrial dysfunction.

Herbal compound "Songyou Yin" reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice.

BACKGROUND: Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches. METHODS: Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects. RESULTS: In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively. CONCLUSION: Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC.

[Treatment of late-staged pancreatic carcinoma with implantation of 125I seeds in combination with regional arterial infusion chemotherapy].

OBJECTIVE: To evaluate the effect of combined use of implantation of (125)I seeds with regional arterial infusion chemotherapy on late-staged pancreatic carcinoma. METHODS: During operation, (125)I seeds were implanted into tumor parenchyma or operative beds for 7 patients with pathological diagnosis of late-staged pancreatic carcinoma, then chemotherapy pump was implanted into common hepatic artery or celiac artery through left gastric artery or right epigastric artery. Gemcitabine (1000 mg/m(2)) plus fluorouracil (500 mg/m(2)) was used for postoperative adjuvant chemotherapy once a week for 7 consecutive weeks. RESULTS: The mean number of implanted (125)I seeds was 42 and the mean dose was 29.4 mCi. The mean follow-up time was 245 days. Rate of pain relief was 100%, metastasis foci was reduced in 2 cases. CA-19-9 Antigen level decreased to normal in all patients. Pancreatic fistula occurred in one case and was cured with conservative therapy. CONCLUSIONS: The combination therapy is effective for late-staged pancreatic carcinoma, it brings symptom relief and improvement in quality of life.