The efficacy and safety of auricular acupuncture versus electroacupuncture in ameliorating chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based regimens.

BACKGROUND: Nausea and vomiting are among the most common and distressing side effects of chemotherapy. Difference in views about the effectiveness of auricular acupuncture (AA) versus electroacupuncture (EA) of chemotherapy-induced nausea and vomiting (CINV) lies at the heart of the debate. The aim of this study is to compare the antiemetic efficacy and safety of AA and EA for CINV. METHODS: One hundred twenty participants, 18 to 75 years old malignant tumors will receiving chemotherapy with cisplatin, will be recruited and randomized into 3 groups equally, Group A (the AA group), Group B (the EA group), and Group C (the control group). The participants in Group A and Group B will receive AA or EA regimens, alternatively, beginning on the day before first day of chemotherapy for a third consecutive cycles. All participants will continue to receive conventional treatment. The incidence and severity of CINV will be assessed using the definition and classification of nausea and vomiting (NCI-CTC AE4.0) and the MASCC (Multinational Association for Supportive Care in Cancer) Antiemesis Tool (MAT). Secondary outcome measures include the degree of abdominal distension, the first time of flatus and defecation, and life quality. Additionally, adverse events will also be documented during the period of the treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness and safety of AA versus EA for CINV following cisplatin-based regimens. TRAIL REGISTRATION: This study is registered with the Chinese Clinical Trial Registry: ChiCTR2000040942.

PRKAA/AMPKα phosphorylation switches the role of RASAL2 from a suppressor to an activator of autophagy.

RASAL2 (RAS protein activator like 2), a RASGTPase activating protein, can catalyze the hydrolysis of RAS-GTP into RAS-GDP to inactivate the RAS pathway in various types of cancer cells. However, the cellular function of RASAL2 remains elusive. Here we showed that RASAL2 can attenuate PRKAA/AMPKα phosphorylation by recruiting phosphatase PPM1B/pp2cß, thus inhibiting the initiation of basal autophagy under normal conditions. In addition, we found that glucose starvation could induce dissociation of PPM1B from RASAL2 and then RASAL2 at S351 be phosphorylated by PRKAA, followed by the binding of phosphorylated-RASAL2 with to PIK3C3/VPS34-ATG14-BECN1/Beclin1 complex to increase PIK3C3 activity and autophagy. Furthermore, RASAL2 S351 phosphorylation facilitated breast tumor growth and correlated to poor clinical outcomes in breast cancer patients. Our study demonstrated that the phosphorylation status of RASAL2 S351 can function as a molecular switch to either suppress or promote AMPK-mediated autophagy. Inhibition of RASAL2 S351 phosphorylation might be a potential therapeutic strategy to overcome the resistance of AMPK-activation agents.Abbreviations: AICAR: aminoimidazole carboxamide ribonucleotide; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ATG14: autophagy related 14; C.C: compound C; CQ: chloroquine; DKO: double-knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PPM1B/pp2cß: protein phosphatase, Mg2+/Mn2+ dependent 1B; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; RASAL2: RAS protein activator like 2; RasGAPs: RasGTPase activating proteins; SQSTM1/p62: sequestosome 1; TNBC: triple-negative breast cancer.

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice.

Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1. Furthermore, replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. The findings imply that ApoE may be essential for body iron homeostasis and also suggest that clinical late-onset diseases with unexplained iron abnormality may partly be related to deficiency or reduced expression of ApoE.

Hepcidin attenuates the iron-mediated secondary neuronal injury after intracerebral hemorrhage in rats.

Iron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins including ferroportin 1 and transferrin receptor 1. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we examined effects of Ad-hepcidin (hepcidin expression adenovirus) on the nonheme iron contents, expression of hepcidin, ferritin and iron transport proteins, neuronal cell survival, water contents in the brain and/or cerebrospinal fluid (CSF), and ICH-induced apoptosis, neurological deficit by RT-PCR, Western blot analysis, NeuN Immunofluorescence, TUNEL, Fluoro-Jade B staining, behavioral performance and Morris water-maze tests in 510 rats. We demonstrated that hepcidin could significantly suppress the ICH-induced increase in iron and ferritin in brain tissues and CSF by inhibiting expression of iron transport proteins, increase neuronal survival by attenuating ICH-induced apoptosis, reactive oxygen species, neurodegeneration and brain edema, as well as effectively improve ICH-induced behavioral and cognitive deficit in rats. The findings collectively showed that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein can potentially be developed into a therapeutic drug for the treatment of ICH patients.

Phosphorylated Rasal2 facilitates breast cancer progression.

BACKGROUND: Rasal2 has diametric effects on progression of oestrogen receptor-positive (ER+) and -negative (ER-) breast cancers. The relevant causes are unknown. It is also unknown whether the effects of Rasal2 are mediated by an exosome-transport process. METHODS: Exosomes were purified from breast cancer cells and identified by transmission electron microscopy and flow cytometry analysis. In vivo and in vitro experiments were conducted to investigate the role of Rasal2 in exosome-mediated breast cancer progression. Western blot analysis was performed to detect Rasal2 and p-Rasal2 (phosphorylated Rasal2) expression in ER+/ER- breast cancer cells and in exosomes, cancer tissues and blood of patients with ER+ or ER- breast cancer. FINDINGS: Phosphorylation of Rasal2 at Serine 237 promoted tumour growth in both ER+ and ER- tumour cells and tissues. The functions of both p-Rasal2 and non-p-Rasal2 (non-phosphorylated-Rasal2) in the modulation of breast cancer progression are exosome-mediated. p-Rasal2 expression in ER+ breast cancer cells and exosomes, cancer tissues and blood was significantly lower than in ER- tumour cells and patients. INTERPRETATION: p-Rasal2 facilitates tumour progression in both ER+ and ER- breast cancers. The ratio of p-Rasal2/non-p-Rasal2 in ER+ and ER- breast cancers is one of the factors deciding the role of Rasal2 (or total Rasal2) as a suppressor in ER+ breast cancers or as a promoter in ER- breast cancers. Targeting the phosphorylation of Rasal2 machinery may therefore be useful as a therapy to restrain breast cancer progression by reducing p-Rasal2/non-p-Rasal2 ratio, especially in ER- breast cancers. FUND: NSFC and Hong Kong Research Grants Council.

[Comparison of Clinical Effects of Electroacupuncture of Abdominal and Limb Acupoints in the Treatment of Acute Pancreatitis].

OBJECTIVE: To compare the difference of therapeutic efficacy of electroacupuncture (EA) stimulation of abdominal acupoints and limb acupoints in the treatment of acute pancreatitis (AP), so as to provide a reference for EA treatment of AP. METHODS: A total of 60 patients with AP were equally and randomly divided into abdominal acupoint group and limb acupoint group. On the basis of retention enema of Chaiqin Chengqi Decoction (containing Radix Bupleurum, Radix Scutellaria, etc.), and abdominal external application of Liuhe Powder ointment (containing Cinnabaris, pearl powder, etc.), patients of the two groups were also treated with acupuncture stimulation of acupoints at the abdomen or limbs. The abdominal acupoints were Shangwan (CV 13), Zhongwan (CV 12), Xiawan(CV 10), Liangmen (ST 21, left), Taiyi(ST 23, left), Chengman (ST 20, left), Fu'ai (SP 16, left), Yindu(KI 19, right), and the limb acupoints were Hegu(LI 4), Neiguan(PC 6), Zusanli(ST 36), Shangjuxu(ST 37), Xiajuxu(ST 39), and Yinlingquan(SP 9) which were punctured with filiform needles by retaining the needles for 30 min after twirling for a while. CV 12 - ST 21, CV 10- SP 16 of the abdomen group, and bilateral PC 6 and ST 36 of the limb group were administered EA (2 Hz/15 Hz, 1 mA and duration of 30 min). The treatment was conducted once daily for 5 days. The abdominal pain severity and distension severity were assessed using the visual analogue scale (VAS), and the abdominal girth was measured by using a soft ruler. RESULTS: Following the treatment, the abdominal pain and distension symptom scores in the lightest and most severe phases of AP and the abdominal girth levels were considerably decreased on the 5th day in the two groups in comparison with their own pre-treatment in the same one group (P < 0.05); and the abdominal pain scores on the 2nd, 3rd and 4th day in the lightest phase, and those on the 2nd, 3rd, 4th and 5th day in the most severe phase were markedly lower in the abdomen acupoint group than in the limb acupoint group (P<0.05). No significant differences were found between two groups in the abdominal distension symptom scores and abdominal circumference levels in the lightest and most severe phases of AP (P>0.05). In addition, no adverse events were found in both groups. CONCLUSION: EA has a good curative effect in the treatment of AP patients. The curative effect of acupuncture of the abdominal acupoints is significantly superior to that of limb acupoints in relieving abdominal pain.

Study of biological activity and targeted distribution of catesbeianalectin in mouse tissue.

Lectin has attracted attention because of its ability to serve as a carrier for targeted drug delivery. Large lectins isolated from marine invertebrates and crustaceans have strong immunogenicity and adverse effects, which limit their usefulness. This study reports the identification of catesbeianalectin via screening a bullfrog skin cDNA library. The catesbeianalectin polypeptide has a molecular weight of 1.47 kD, making it the smallest known lectin in terms of molecular weight. Circular dichroism analysis showed a PPII helix secondary structure. Catesbeianalectin strongly induces agglutination of rabbit erythrocytes and a variety of pathogens include Staphylococcus aureus, Streptococcus suis type 2, Actinobacillus pleuropneumoniae, and piglet paratyphoid Salmonella. The mean serum titer in catesbeianalectin-immunized Balb/c mice was 1:25, which was significantly lower than that of positive controls immunized with wheat germ agglutinin. Surface plasmon resonance indicated an S-type lectin. 125I-labeled catesbeianalectin did not pass the blood-brain barrier. This study provides a basis for further research on the potential of catesbeianalectin as a carrier in targeted drug delivery.

[Observation on the Efficacy of Electroacupuncture for Functional Constipation].

OBJECTIVE: To investigate the therapeutic rule of electroacupuncture (EA) in treating functional constipation. METHODS: Eighty-eight patients with severe chronic functional constipation were randomized divided into EA (n=45) and sham-EA (n=43) groups. Patients in the EA group were treated with EA at bilateral Tianshu (ST 25), Fujie (SP 14), Shangjuxu (ST 37), and those in the sham-EA group were received superficial acupuncture at 1 cun lateral to the identical acupoints without electrical current delivery. The number of patients with complete spontaneous bowel movements (CSBM) was weekly compared between the EA and sham-EA groups at baseline week, during 8 weeks' treatment, as well as the follow-up 4th, 8th and 12th weeks after treatment. The Bristol Stool Chart (BSC) and defecation difficulty scores were also weekly compared from baseline until 8 weeks. RESULTS: The CSBM showed significant differences from 3 to 8 weeks and at 4th, 8th and 12th weeks post-treatment (P<0.05), but not within the first two weeks between the EA and sham-EA groups. The number of patients who had more than 3 times of CSBM per week was increased in the EA group(P<0.05). The therapeutic effect of EA group was superior to that of the sham-EA group in improving BSC over the 4th and 5th weeks (P<0.05). The defecation difficulty score was improved in the EA group than in the sham-EA group since the 4th week (P<0.05). CONCLUSIONS: EA shows therapeutic effect for functional constipation by improving CSBM and BSC.

Electroacupuncture for the prevention of postoperative gastrointestinal dysfunction in participants undergoing vascular laparotomy under general anesthesia: a randomized controlled trial.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is a common complication following laparotomy under general anesthesia (GA). Abdominal distension occurs in 8-28% of surgeries within 24 h postoperatively. The present study aimed to analyze the efficacy of electroacupuncture (EA) for the prevention of PGD by applying preoperative EA stimulation of PC6 (Neiguan), ST36 (Zusanli), and ST37 (Shangjuxv) bilaterally twice within 24 h prior to surgery, compared with no acupuncture treatment. METHODS: The study participants were assessed and selected from participants undergoing vascular laparotomy under GA at the Liver and Vascular Surgery Unit in West China Hospital of Sichuan University. The selected participants were randomly allocated to two groups: routine-treatment (RT) and EA group receiving EA at PC6, ST36, and ST37. A computer-generated list of random numbers was used to determine the allocation of the participants, with numbered opaque sealed envelopes containing the randomization schedule. Eligible participants were all adults aged 18 years or above who were scheduled to undergo vascular laparotomy under GA within 24 h and had no history of EA treatment. The exclusion criteria included participants with serious systemic disease and history of EA treatment. While the RT group received standard treatments, the EA group received additional EA treatments. During each treatment session, EA stimulation was performed for a duration of 20 min at a frequency of 15 Hz with a continuous wave. All such participants received two EA treatments within 24 h before surgery. The outcomes were measured in three metrics: incidence and degree of abdominal distension; first times of flatus and defecation; and duration of hospitalization. RESULTS: Forty-three participants were recruited, of whom 42 participants successfully completed the study. Each group contained 21 participants. The incidence of abdominal distension (42.8, 76.2%) and degree of abdominal distension were significantly reduced in the EA group (P = 0.03 and P = 0.03, respectively). In comparisons of the first times of flatus (3.05 ± 0.58, 3.29 ± 0.42 days) and defecation (2.81 ± 0.51, 3.20 ± 0.55 days) and duration of hospitalization (5.33 ± 0.68, 5.75 ± 0.66 days), the EA group was superior to the RT group to some extent (P = 0.13, P = 0.02, and P = 0.04, respectively). CONCLUSIONS: Preoperative EA at PC6, ST36, and ST37 might be useful for preventing PGD, thereby improving gastrointestinal function recovery. Trial registration This study is registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003649.

Electroacupuncture for the prevention of postoperative gastrointestinal dysfunction in patients undergoing vascular surgery under general anesthesia: study protocol for a prospective practical randomized controlled trial.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications following major surgeries under general anesthesia (GA). Despite ongoing research and new drug treatments, abdominal distension within 24 h postoperatively occurs in 8%-28% of all surgeries. We aim to analyze the effectiveness of preventing PGD by preoperatively stimulating Neiguan (PC6), Zusanli (ST36) and Shangjuxu (ST37) bilaterally twice a day compared with sham-acupuncture treatment and standard treatment. METHODS AND DESIGN: This is a single-center, prospective practical randomized controlled trial. All groups will be given standard treatments. Patients undergoing vascular surgery under GA will be included from the Vascular Surgery Unit in West China Hospital of Sichuan University, China, and divided into three groups. The experimental group will receive routine treatments and acupuncture at PC6, ST36 and ST37 bilaterally with electrical stimulation twice a day for 20 min preoperatively. The sham-acupuncture group will receive pseudo-electroacupuncture at sham acupoints of PC6, ST36 and ST37, which are 1 cun away from the real acupoints. The routine-treatment group will not receive electroacupuncture. The outcomes include the incidence of abdominal distention, abdominal circumference, the degree of abdominal distension, the first time of flatus and defecation, and hospitalization duration. DISCUSSION: The results from this study will demonstrate whether preoperative electroacupuncture is an effective method for the prevention of PGD in patients undergoing vascular surgery under GA. This study may also provide a standardized acupuncture treatment for reduction of PGD.