A preliminary study on the diversity of butyrate-producing bacteria in response to the treatment of depression with Xiaoyaosan.

Butyrate-producing bacteria generate butyrate, which has antidepressant effects. Xiaoyaosan (XYS), a traditional Chinese medicine (TCM) used to treat depression, may improve depression-like behaviour by modulating the gut microbiota. However, the functional groups and mechanisms of action in the XYS treatment of depression remain unknown. This study aimed to analyse with clone sequencing the changes in intestinal butyrate-producing bacteria in XYS-treated chronic unpredictable mild stress (CUMS) rats. We successfully established the XYS-treated CUMS rat model of depression. Rat faecal samples were collected before, during, and after the experiment, and butyryl-CoA:acetate CoA-transferase gene primers were selected for PCR amplification to determine the diversity of butyrate-producing bacteria. The results showed that XYS increased intestinal butyrate-producing bacterial diversity in CUMS rats regarding phylum and genus numbers; the number of phyla increased to two, distributed in Firmicutes and Bacteroides, and four genera were distributed in Eubacterium sp., Roseburia sp., Clostridium sp. and Bacteroides sp. Only one phylum and two genera were present in the model group without XYS treatment. Our findings indicate that XYS can improve depression-like behaviour by regulating intestinal butyrate-producing bacteria diversity, particularly Roseburia sp. and Eubacterium sp., thus providing new insights into the targeted regulation of the intestinal flora to treat depression.

Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa.

AIMS: The study aimed to perform a systematic investigation of the effects of quercetin on biofilm formation and virulence factors in Pseudomonas aeruginosa. METHODS AND RESULTS: The Ps. aeruginosa strain PAO1 was selected as the test strain. The results indicated that quercetin did not impact the growth of PAO1 as determined by MIC and growth curve analysis. However, this compound significantly inhibited (P < 0·05) biofilm formation and production of virulence factors including pyocyanin, protease and elastase at a lower concentration than those for most previously reported plant extracts and substances. Considering the central role of quorum sensing (QS) in the regulation of biofilm and virulence factor, we further detected the transcriptional changes associated with QS and found that the expression levels of lasI, lasR, rhlI and rhlR were significantly reduced (P < 0·05) by 34, 68, 57 and 50%, respectively, in response to 16 µg ml(-1) quercetin. CONCLUSIONS: This study indicated that quercetin is an effective inhibitor of biofilm formation and virulence factors in Ps. aeruginosa. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to demonstrate that quercetin is an effective inhibitor of QS, biofilm formation and virulence factors in Ps. aeruginosa. Furthermore, quercetin might have potential in fighting biofilm-related infections.

Perioperative acupuncture modulation: more than anaesthesia.

Accumulated evidences from clinical trials and updated reviews suggest that the role of acupuncture in perioperative medicine extends beyond the classical scope of anaesthesia and has been underestimated. Perioperative acupuncture reduces not only the consumption of anaesthetics and analgesics, but also anaesthesia-related complications, and protects organs in the perioperative period. These beneficial effects make acupuncture a promising approach in perioperative management, especially with respect to enhanced surgery recovery and specific surgical populations, such as elderly patients and 'triple-low' patients. Furthermore, efforts have been made to optimize the clinical application of perioperative acupuncture.

The effect of pre-treatment with transcutaneous electrical acupoint stimulation on the quality of recovery after ambulatory breast surgery: a prospective, randomised controlled trial.

Electroacupuncture has been demonstrated to be effective at alleviating pain and postoperative side-effects. Our aim was to investigate whether transcutaneous electric acupoint stimulation, a low-skill alternative to needle-based electroacupuncture, could improve the quality of recovery after ambulatory surgery. Seventy-two women scheduled for cosmetic breast surgery were randomly allocated to transcutaneous electric acupoint stimulation or sham groups. Patients in the transcutaneous electric acupoint stimulation group received 30 min of electrical stimulation at three acupoints located on the hand and forearm before the induction of general anaesthesia. We found significant mean (SD) differences between the transcutaneous electric acupoint stimulation and sham groups in the mean (SD) length of recovery room stay (35.6 (12.9) min vs 48.3 (16.3) min, p = 0.01), time to removal of the laryngeal mask airway (10.2 (2.5) min vs 17.8 (4.4) min, p = 0.01), and time to reorientation of the patient (14.6 (3.2) min vs 26.5 (5.0) min, p = 0.01). Further, postoperative pain scores and the incidence of side-effects were all lower in the transcutaneous electric acupoint stimulation group. In conclusion, transcutaneous electric acupoint stimulation can significantly improve the quality of recovery and decrease the incidence of anaesthesia-related side-effects for patients undergoing ambulatory surgery.

In vivo delivery of bovine viral diahorrea virus, E2 protein using hollow mesoporous silica nanoparticles.

Our work focuses on the application of mesoporous silica nanoparticles as a combined delivery vehicle and adjuvant for vaccine applications. Here we present results using the viral protein, E2, from bovine viral diarrhoea virus (BVDV). BVDV infection occurs in the target species of cattle and sheep herds worldwide and is therefore of economic importance. E2 is a major immunogenic determinant of BVDV and is an ideal candidate for the development of a subunit based nanovaccine using mesoporous silica nanoparticles. Hollow type mesoporous silica nanoparticles with surface amino functionalisation (termed HMSA) were characterised and assessed for adsorption and desorption of E2. A codon-optimised version of the E2 protein (termed Opti-E2) was produced in Escherichia coli. HMSA (120 nm) had an adsorption capacity of 80 µg Opti-E2 per mg HMSA and once bound E2 did not dissociate from the HMSA. Immunisation studies in mice with a 20 µg dose of E2 adsorbed to 250 µg HMSA was compared to immunisation with Opti-E2 (50 µg) together with the traditional adjuvant Quillaja saponaria Molina tree saponins (QuilA, 10 µg). The humoral responses with the Opti-E2/HMSA nanovaccine although slightly lower than those obtained for the Opti-E2 + QuilA group demonstrated that HMSA particles are an effective adjuvant that stimulated E2-specific antibody responses. Importantly the cell-mediated immune responses were consistently high in all mice immunised with Opti-E2/HMSA nanovaccine formulation. Therefore we have shown the Opti-E2/HMSA nanoformulation acts as an excellent adjuvant that gives both T-helper 1 and T-helper 2 mediated responses in a small animal model. This study has provided proof-of-concept towards the development of an E2 subunit nanoparticle based vaccine.

Transcutaneous electric acupoint stimulation reduces intra-operative remifentanil consumption and alleviates postoperative side-effects in patients undergoing sinusotomy: a prospective, randomized, placebo-controlled trial.

BACKGROUND: Although opioids are widely used as analgesics in general anaesthesia, they have unpleasant side-effects and can delay postoperative recovery. Acupuncture and related techniques are effective for acute and chronic pain, and reduces some side-effects. We assessed the effect of transcutaneous electric acupoint stimulation (TEAS) on intra-operative remifentanil consumption and the incidences of anaesthesia-related side-effects. METHODS: Sixty patients undergoing sinusotomy were randomly assigned to TEAS or control group. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) before anaesthesia. The patients in the control group had the electrodes applied, but received no stimulation. Bispectral index was used to monitor the depth of anaesthesia. Perioperative haemodynamics were recorded, and peripheral blood samples were collected to measure the levels of mediators of surgical stress. The primary end point was intraoperative remifentanil consumption and the secondary endpoints were recovery quality and anaesthesia-related side-effects. RESULTS: Patients in the TEAS group required 39% less remifentanil during surgery than controls [0.0907 (SD 0.026) µg kg(-1) min(-1) vs 0.051 (0.018) µg kg(-1) min(-1)]. There were no differences in intra-operative haemodynamics or surgical stress between groups. However, the time to extubation and recall in the control group was 16.8 (6.8) min and 23.0 (5.0) min, respectively, significantly longer than that in the TEAS group (P<0.01). TEAS also decreased the incidence of dizziness and pruritus within the first 24 h after surgery (P<0.01). CONCLUSION: The use of TEAS significantly reduced intra-operative remifentanil consumption and alleviated postoperative side-effects in patients undergoing sinusotomy. CLINICAL TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01700855).

Hyperbaric oxygen therapy attenuates neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients.

BACKGROUND: Neuropathic pain after nerve injury is severe and intractable, and current drug and non-drug therapies offer very limited pain relief. Hyperbaric oxygen (HBO 2) has been clinically used for protection of the nervous system after acute injury. We investigated whether HBO 2 treatment could prevent and/or attenuate neuropathic pain in animals and in patients. METHODS: Mechanical allodynia and thermal hyperalgesia and neurochemical alterations of neuropathic pain were analysed in male, adult, Sprague-Dawley rats with sciatic nerve injury. Clinical trials were conducted in patients with idiopathic trigeminal neuralgia. RESULTS: Repetitive HBO 2 treatment [a combination of pressure at 3 atmosphere absolute (ATA) and pure oxygen] greatly inhibited behavioural signs of neuropathic pain manifested as thermal hyperalgesia and mechanical allodynia. Such an HBO 2 treatment also inhibited nerve injury-induced induction of c-Fos and activation of astrocytes and increased phosphorylation of NR2B receptor and the subsequent Ca 2+-dependent signals in rats. Neither high pressure (up to 3 ATA) nor pure oxygen alone resulted in analgesic effect. In clinical trials, one course of HBO 2 therapy (10 consecutive days) produced a rapid-onset, dose-dependent and long-lasting analgesic effects evidenced by the decreased doses of carbamazepine required for keeping patient pain at a minimum and decreased scores of visual analogue scales, which was used for patient's self-evaluation. CONCLUSIONS: These findings support that HBO 2 therapy is an effective approach for treating neuropathic pain in both animals and human beings and suggest that neural protection, anti-inflammation and inhibition of nerve injury-induced altered neural activity may contribute to the analgesic effect of HBO 2 therapy.

Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia.

We previously found that ginsenoside Rd (Rd), one of the major active ingredients in Panax ginseng, protects neuronal cells from hydrogen peroxide and oxygen-glucose deprivation, an in vitro model of cerebral ischemia. In this study, we examined the protective effects of Rd in an animal model of focal cerebral ischemia. Rats administered with Rd or vehicle were subjected to transient middle cerebral artery occlusion (MCAO). Rd (50 mg/kg) significantly reduced the infarct volume by 52.8%. This reduction of injury volume was associated with an improvement in neurological function and was sustained for at least 2 weeks after the induction of ischemia. To evaluate the underlying mechanisms of Rd against stroke, brain tissues were assayed for mitochondrial enzyme activities, mitochondrial membrane potential (MMP), production of reactive oxygen species (ROS), energy metabolites, and apoptosis. Rd markedly protected mitochondria as indicated by preserved respiratory chain complex activities and aconitase activity, lowered mitochondrial hydrogen peroxide production, and hyperpolarized MMP. Microdialysis results illustrated that Rd significantly decreased the accumulation of lactate, the end product of anaerobic glycolysis, and increased pyruvate, the end product of aerobic glycolysis, hence inducing a lower lactate/pyruvate ratio. Additionally, in vitro studies further exhibited that Rd protected isolated mitochondria from calcium-induced damage by attenuating mitochondrial swelling, preserving MMP and decreasing ROS production. Moreover, Rd treatment reduced mitochondrial release of cytochrome c (CytoC) and apoptosis-inducing factor (AIF), thereby minimizing mitochondria-mediated apoptosis following ischemia. In conclusion, these findings demonstrated that Rd exerts neuroprotective effects in transient focal ischemia, which may involve an integrated process of the mitochondrial protection, energy restoration and inhibition of apoptosis.

The Arabidopsis HOS1 gene negatively regulates cold signal transduction and encodes a RING finger protein that displays cold-regulated nucleo--cytoplasmic partitioning.

Low temperature is one of the most important environmental stimuli that control gene transcription programs and development in plants. In Arabidopsis thaliana, the HOS1 locus is a key negative regulator of low temperature-responsive gene transcription. The recessive hos1 mutation causes enhanced induction of the CBF transcription factors by low temperature as well as of their downstream cold-responsive genes. The hos1 mutant plants flower early, and this correlates with a low level of Flowering Locus C gene expression. The HOS1 gene was isolated through positional cloning. HOS1 encodes a novel protein with a RING finger motif near the amino terminus. HOS1 is ubiquitously expressed in all plant tissues. HOS1--GFP translational fusion studies reveal that HOS1 protein resides in the cytoplasm at normal growth temperatures. However, in response to low temperature treatments, HOS1 accumulates in the nucleus. Ectopic expression of HOS1 in wild-type plants causes cosuppression of HOS1 expression and mimics the hos1 mutant phenotypes.

Hyperbaric oxygen preconditioning induces neuroprotection against ischemia in transient not permanent middle cerebral artery occlusion rat model.

OBJECTIVE: This study was designed to determine if repeated hyperbaric oxygen (HBO) exposure induces ischemic tolerance in focal cerebral ischemia. METHODS: Sixty male SD rats were used in this study. Thirty animals underwent transient middle cerebral artery occlusion (MCAO) and the other thirty permanent MCAO model. The rats were randomly allocated to 3 sub-groups: control group (n = 10), HBO-3 group (n = 10), and HBO-5 group (n = 10). The animals in HBO-3 and HBO-5 groups received 1 hour hyperbaric oxygenation at 2.5 atmosphere absolute (ATA) in 100% oxygen every day for 3 and 5 days, respectively. The animals in the control group received sham treatments. 24 hours after the last HBO, transient MCAO (120 min) and permanent MCAO were induced by introducing a 3-0 nylon monofilament suture through internal carotid artery based on the Koizumi technique. The neurological outcome was evaluated until 24 hours after reperfusion in transient MCAO rats and ischemia in permanent MCAO rats. The infarct volume was then assessed by TTC staining. RESULTS: In transient MCAO rats, the neurological outcome in both the HBO-3 and HBO-5 groups was better than that of the control group (P < 0.05 and 0.001). The infarct volume decreased from 171.5 +/- 113 mm3 to 40.6 +/- 49.9 mm3(P < 0.05) in the HBO-3 group and 16.2 +/- 28.8 mm3(P < 0.01) in the HBO-5 group. There were no significant differences in neurological outcome and infarct volume among the three groups in permanent MCAO rats. CONCLUSIONS: The present study demonstrated that HBO preconditioning can induce ischemic tolerance in transient not permanent MCAO rats in a "dose-dependent" manner.

[Therapeutic effect of combined therapy of Salvia miltiorrhizae and Polyporus umbellatus polysaccharide in the treatment of chronic hepatitis B].

90 patients of chronic hepatitis B with positive HBV replication markers and abnormality of ALT were randomly allocated to 3 groups. 30 cases were treated with Salvia miltiorrhizae (SM) and Polyporus Umbellatus polysaccharide (PUP) as group I, 30 cases were treated with SM solely as group II and 30 cases were treated with PUP only as group III. By the end of 3 months in the treatment course, normalization rate of ALT were 80.0%, 40.0% and 53.3% and the negative conversion rate of HBeAg were 56.7%, 50.0% and 16.7% in the group I, II and III respectively. Follow up for 3 months after the end of therapy, ALT level was normal in 82.6%, 42.7% and 59.1% respectively. HBeAg was negative in 60.9%, 52.4% and 22.7%. Follow up for 9 months after the end of the treatment, ALT was normal in 83.3%, 43.8% and 56.3%. HBeAg was negative in 66.7%, 56.3% and 25.0% respectively. These results showed that combined therapy with SM and PUP might be more potent than SM and PUP therapy alone.