Luhong Formula Has a Cardioprotective Effect on Left Ventricular Remodeling in Pressure-Overloaded Rats.

BACKGROUND: Luhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. METHODS: Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-ß1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-ß1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. RESULTS: LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression. CONCLUSION: LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

Anti-inflammatory effect of up-regulated microRNA-221-3p on coronary heart disease via suppressing NLRP3/ASC/pro-caspase-1 inflammasome pathway activation.

OBJECTIVE: As some evidence has demonstrated the role of microRNA-221 (miR-221) on coronary heart disease (CHD), the aim of the present study was to investigate the effect of miR-221-3p on CHD via regulating NLRP3/ASC/pro-caspase-1 inflammasome pathway. METHODS: Sixty CHD patients and 60 healthy controls were collected to detect the expression of miR-221-3p, NLRP3, ASC, pro-caspase-1 in peripheral blood and the contents of related factors in serum. The rats model of CHD was injected with miR-221-3p agomir or miR-221-3p antagomir to explore its functions in miR-221-3p, NLRP3, ASC and pro-caspase-1 expression, electrocardiogram data, cardiomyocytes apoptosis, myocardial injury, inflammatory reaction and oxidative stress of CHD rats. RESULTS: MiR-221-3p declined and NLRP3, ASC and pro-caspase-1 raised in CHD. Up-regulated miR-221-3p reduced the change value of J-point and T-wave, decreased NLRP3, ASC and pro-caspase-1 expression, suppressed apoptosis in cardiomyocytes, as well as suppressed myocardial injury, inflammatory reaction and oxidative stress in CHD rats. CONCLUSION: This study highlights that up-regulated miR-221-3p suppresses the overactivation of NLRP3/ASC/pro-caspase-1 inflammasome pathway and has an anti-inflammatory effect in CHD. Thus, miR-221-3p may serve as a potential target for the treatment of CHD.

Luhong Granules Prevent Ventricular Remodelling after Myocardial Infarction by Reducing the Metabolites TMAO and LPS of the Intestinal Flora.

BACKGROUND: Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. PURPOSE: In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. METHODS: Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg-1·d-1), vancomycin (0.075 g·ml-1·d-1), and 0.9% saline (5 ml·kg-1·d-1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). RESULTS: H&E and Masson's trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P < 0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P < 0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P < 0.05). CONCLUSIONS: Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.

Upregulation of long noncoding RNA RP4 exacerbates hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3/Wnt/ß-catenin pathway.

This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O2 concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/ß-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/ß-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/ß-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury.

Performance evaluation of the Personal Mobility and Manipulation Appliance (PerMMA).

The Personal Mobility and Manipulation Appliance (PerMMA) is a recently developed personal assistance robot created to provide people with severe physical disabilities enhanced assistance in both mobility and manipulation. PerMMA aims to improve functional independence when a personal care attendant is not available on site. PerMMA integrates both a smart powered wheelchair and two dexterous robotic arms to assist its users in completing essential mobility and manipulation tasks during basic and instrumental activities of daily living (ADL). Two user interfaces were developed: a local control interface and a remote operator controller. This paper reports on the evaluation of PerMMA with end users completing basic ADL tasks. Participants with both lower and upper extremity impairments (N=15) were recruited to operate PerMMA and complete up to five ADL tasks in a single session of no more than two hours (to avoid fatigue or frustration of the participants). The performance of PerMMA was evaluated by participants completing ADL tasks with two different control modes: local mode and cooperative control. The users' task completion performance and answers on pre/post-evaluation questionnaires demonstrated not only the ease in learning and usefulness of PerMMA, but also their attitudes toward assistance from advanced technology like PerMMA. As a part of the iterative development process, results of this work will serve as supporting evidence to identify design criteria and other areas for improvement of PerMMA.

Planning Fireworks Trajectories for Steerable Medical Needles to Reduce Patient Trauma.

Accurate insertion of needles to targets in 3D anatomy is required for numerous medical procedures. To reduce patient trauma, a "fireworks" needle insertion approach can be used in which multiple needles are inserted from a single small region on the patient's skin to multiple targets in the tissue. In this paper, we explore motion planning for "fireworks" needle insertion in 3D environments by developing an algorithm based on Rapidly-exploring Random Trees (RRTs). Given a set of targets, we propose an algorithm to quickly explore the configuration space by building a forest of RRTs and to find feasible plans for multiple steerable needles from a single entry region. We present two path selection algorithms with different optimality considerations to optimize the final plan among all feasible outputs. Finally, we demonstrate the performance of the proposed algorithm with a simulation based on a prostate cancer treatment environment.

3D Motion Planning Algorithms for Steerable Needles Using Inverse Kinematics.

Steerable needles can be used in medical applications to reach targets behind sensitive or impenetrable areas. The kinematics of a steerable needle are nonholonomic and, in 2D, equivalent to a Dubins car with constant radius of curvature. In 3D, the needle can be interpreted as an airplane with constant speed and pitch rate, zero yaw, and controllable roll angle.We present a constant-time motion planning algorithm for steerable needles based on explicit geometric inverse kinematics similar to the classic Paden-Kahan subproblems. Reachability and path competitivity are analyzed using analytic comparisons with shortest path solutions for the Dubins car (for 2D) and numerical simulations (for 3D). We also present an algorithm for local path adaptation using null-space results from redundant manipulator theory. Finally, we discuss several ways to use and extend the inverse kinematics solution to generate needle paths that avoid obstacles.