Design and implementation of a highly integrated dual hemisphere capsule robot.

To achieve cancer screening in any appointed position in 3D regions of the gastrointestinal (GI) tract such as esophagus, stomach and colon, a highly integrated dual hemisphere capsule robot (DHCR) with a novel three-layer nested structure is proposed. Based on tracking effect, in which the robotic axis is likely to be approximately coincident with the orientation of the space universal rotating magnetic field (SURMF) using the gyroscope dynamic balance, the dual hemisphere structure realizes the observation at a fixed-point in the passive mode and the rolling locomotion in the active mode by the dynamic posture control of the SURMF manipulation. The image acquisition module, wireless transmission module and driving actuator are tuned in a spherical structure, making the DHCR more compact and less invasive. To verify the maneuverability of the innovative DHCR both for observation at a fixed-point and navigation in curved intestine by aid of image, experiments are conducted in the simulated GI tract environment. The results show that the DHCR achieves effective conversion between posture adjustment and rolling locomotion, which lays a foundation for all-over inspection and medical operation inside 3D regions of the GI tract of human body.

Posture Dynamic Modeling and Stability Analysis of a Magnetic Driven Dual-Spin Spherical Capsule Robot.

In order to realize the intervention operation in the unstructured and ample environments such as stomach and colon, a dual-spin spherical capsule robot (DSCR) driven by pure magnetic torque generated by the universal rotating magnetic field (URMF) is proposed. The coupled magnetic torque, the viscoelastic friction torque, and the gravity torque were analyzed. Furthermore, the posture dynamic model describing the electric-magnetic-mechanical-liquid coupling dynamic behavior of the DSCR in the gastrointestinal (GI) tract was established. This model is a second-order periodic variable coefficient dynamics equation, which should be regarded as an extension of the Lagrange case for the dual-spin body system under the fixed-point motion, since the external torques were applied. Based on the Floquet-Lyapunov theory, the stability domain of the DSCR for the asymptotically stable motion and periodic motion were obtained by investigating the influence of the angular velocity of the URMF, the magnetic induction intensity, and the centroid deviation. Research results show that the DSCR can realize three kinds of motion, which are asymptotically stable motion, periodic motion, and chaotic motion, according to the distribution of the system characteristic multipliers. Moreover, the posture stability of the DSCR can be improved by increasing the angular velocity of the URMF and reducing the magnetic induction intensity.

Astragaloside IV protects against the pathological cardiac hypertrophy in mice.

Although pathologic hypertrophic hearts currently maintain output, sustained cardiac hypertrophy could predispose a patient to arrhythmia and sudden death, and also cause heart failure. Thus, finding effective treatment and exploring the underlying molecular mechanisms of cardiac hypertrophy is urgently necessary. Astragaloside IV (AST-IV) is the main active component, extracted from the traditional Chinese medicinal herb Astragalus membranaceus. Previous studies have indicated that AST-IV has various bioactivities, such as anti-cancer, anti-oxidative stress and anti-inflammation. In the present study, we aimed to explore the effects of AST-IV on cardiac hypertrophy induced by aortic banding (AB) surgery in mice, and to reveal the underlying signaling mechanisms. The suppressor of IKKε (SIKE) is a negative regulator of the interferon pathway, which could be enhanced by AST-IV to ameliorate pathological cardiac hypertrophy in mice through inactivating TANK-binding kinase 1 (TBK1)/PI3K/AKT signaling pathway. AST-IV attenuated cardiac hypertrophy, collagen accumulation and abnormal cardiac functions. In addition, AB-induced apoptosis and inflammation in the heart tissue samples of mice, which were attenuated by AST-IV administration through inhibiting SIKE expression levels. Together, the findings above indicated that AST-IV might be a potential candidate to prevent cardiac hypertrophy via elevating SIKE to suppress TBK1/PI3K/AKT activity.

Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice.

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Induction of apoptosis in HCT-116 colon cancer cells by polysaccharide of Larimichthys crocea swim bladder.

Larimichthys crocea swim bladder is a traditional food and medicine widely used in China. The in vitro anticancer effects of polysaccharide of L. crocea swim bladder (PLCSB) in HCT-116 human colon cancer cells was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. At concentrations ranging between 0 and 800 µg/ml PLCSB, cancer cell viability was decreased by PLCSB in a concentration-dependent manner. In particular, 400 µg/ml PLCSB significantly (P<0.05) induced apoptosis, which was demonstrated by 4,6-diamidino-2-phenylindole staining and flow cytometry analysis. To elucidate the mechanisms underlying the anticancer effect of PLCSB in HCT-116 cancer cells, the expression of apoptosis and metastasis-associated genes was analyzed by reverse transcription-polymerase chain reaction and western blot analysis. A total of 400 µg/ml PLCSB significantly induced apoptosis in HCT-116 cells (P<0.05) via the upregulation Bax, p53, p21, apoptotic protease activating factor 1, caspase-3, -8, and -9, as well as Fas and the downregulation of B-cell lymphoma 2 (Bcl-2), Bcl-extra large and Fas ligand (L). The results of this study demonstrated that PLCSB exhibits an anticancer effect on HCT-116 colon cancer cells, in vitro.

Preventive effect of Lactobacillus fermentum Lee on activated carbon-induced constipation in mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Lee (LF-Lee) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered lactic acid bacteria for nine days. Body weight, dietary and water intake, defecation status, gastrointestinal (GI) transit and defecation time, as well as levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were measured to evaluate the preventive effects of LF-Lee on constipation. Bisacodyl, a laxative drug, was administered as a positive control. The time taken until the first defecation of a black stool for normal, control, bisacodyl- (100 mg/kg, oral administration), Lactobacillus bulgaricus (LB)-, LF-Lee low dose (L)- and LF-Lee high dose (H)-treated mice was 90, 218, 117, 180, 161 and 151 min, respectively. Following the consumption of LB, LF-Lee (L) or LF-Lee (H), or the oral administration of bisacodyl, the GI transit was reduced to 55.2, 65.8, 73.1 and 94.6%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and those of SS were reduced in the mice treated with LF-Lee compared with those in the untreated control mice (P<0.05). These results demonstrate that lactic acid bacteria have preventive effects on constipation in mice and that LF-Lee has superior functional activity.

Therapeutic effect of activated carbon-induced constipation mice with Lactobacillus fermentum Suo on treatment.

The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription-polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity.

CTLA4-Ig relieves inflammation in murine models of coxsackievirus B3-induced myocarditis.

BACKGROUND: T-cell-mediated cellular immunity is one of the most important factors in viral myocarditis. As an important costimulatory molecule, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) alleviates autoimmunity by influencing the balance of helper T cell (T(H)) subtype 1 (T(H)1) to T(H)2 in autoimmune diseases. The effects and mechanisms of CTLA4 fusion protein (CTLA4-Ig) in mice with coxsackievirus B3 (CVB3)-induced myocarditis were investigated. METHODS: BALB/c mice were randomly divided into a CVB3 group, an IgG group, a CTLA4-Ig group, and a group of healthy control mice. Mice were humanely killed on day 7 post CVB3 inoculation, then CVB3, IFN-γ, mouse IL-4 (mIL-4), and mouse IL-2 (mIL-2) expression in myocardium were examined by real-time quantitative polymerase chain reaction, and the serum concentrations of IFN-γ, mIL-4, and mIL-2 were measured by enzyme-linked immunosorbent assay. RESULTS: IFN-γ expression was significantly higher and mIL-4 levels in serum were lower in the CVB3 group when compared with those in the healthy control group (P < 0.01). In the CTLA4-Ig group, the mouse mortality and CVB3 mRNA in myocardium were reduced compared with those in the CVB3 group. Furthermore, IFN-γ expression was lower, and mIL-4 was significantly higher compared with those values in the CVB3 and the IgG groups. The levels of mIL-2 in all groups showed no statistical difference (P > 0.05). CONCLUSIONS: T(H)1 cytokines were predominant in the acute phase of viral myocarditis. CTLA4-Ig relieves myocardial inflammation, virus replication, and mouse mortality, probably by influencing the balance of T(H)1 to T(H)2.