[Mechanism of tonifying Qi by traditional Chinese medicine from mitochondrial dynamics].

According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.

Bayesian analysis of coupled cellular and nuclear trajectories for cell migration.

Cell migration, the process by which cells move from one location to another, plays crucial roles in many biological events. While much research has been devoted to understand the process, most statistical cell migration models rely on using time-lapse microscopy data from cell trajectories alone. However, the cell and its associated nucleus work together to orchestrate cell movement, which motivates a joint analysis of coupled cell-nucleus trajectories. In this paper, we propose a Bayesian hierarchical model for analyzing cell migration. We incorporate a bivariate angular distribution to handle the coupled cell-nucleus trajectories and introduce latent motility status indicators to model a cell's motility as a time-dependent characteristic. A Markov chain Monte Carlo algorithm is provided for practical implementation of our model, which is used on real experimental data from MDA-MB-231 and NIH 3T3 cells. Through the fitted models, deeper insights into the migratory patterns of these experimental cell populations are gained and their differences are quantified.

Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology.

NAC1, a BTB/POZ family member, has been suggested to participate in maintaining the stemness of embryonic stem cells and has been implicated in the pathogenesis of human cancer. In ovarian cancer, NAC1 upregulation is associated with disease aggressiveness and with the development of chemoresistance. Like other BTB/POZ proteins, NAC1 forms discrete nuclear bodies in non-dividing cells. To investigate the biological role of NAC1 nuclear bodies, we characterized the expression dynamics of NAC1 nuclear bodies during different phases of the cell cycle. Fluorescence recovery after photobleaching assays revealed that NAC1 was rapidly exchanged between the nucleoplasm and NAC1 nuclear bodies in interphase cells. The number of NAC1 bodies significantly increased and their size decreased in the S phase as compared to the G0/G1 and G2 phases. NAC1 nuclear bodies disappeared and NAC1 became diffuse during mitosis. NAC1 nuclear bodies reappeared immediately after completion of mitosis. These results indicate that a cell cycle-dependent regulatory mechanism controls NAC1 body formation in the nucleus and suggest that NAC1 body dynamics are associated with mitosis or cytokinesis.

Decomposition of cell activities revealing the role of the cell cycle in driving biofunctional heterogeneity.

Heterogeneity of cell phenotypes remains a barrier in progressing cell research and a challenge in conquering cancer-related drug resistance. Cell morphology, the most direct property of cell phenotype, evolves along the progression of the cell cycle; meanwhile, cell motility, the dynamic property of cell phenotype, also alters over the cell cycle. However, a quantifiable research understanding the relationship between the cell cycle and cell migration is missing. Herein, we coordinate the migratory behaviours of NIH 3T3 fibroblasts to their corresponding phases of the cell cycle, the G1, the S, and the G2 phases, and explain the relationship through the spatiotemporal arrangements between the Rho GTPases' signals and cyclin-dependent kinase inhibitors, p21Cip1, and p27Kip1. Taken together, we demonstrate that both cell morphology and the dynamic subcellular behaviour are homogenous within each stage of the cell cycle phases but heterogenous between phases through quantitative cell analyses and an interactive molecular mechanism between the cell cycle and cell migration, posing potential implications in countering drug resistance.

Analysis of video-based microscopic particle trajectories using Kalman filtering.

The fidelity of the trajectories obtained from video-based particle tracking determines the success of a variety of biophysical techniques, including in situ single cell particle tracking and in vitro motility assays. However, the image acquisition process is complicated by system noise, which causes positioning error in the trajectories derived from image analysis. Here, we explore the possibility of reducing the positioning error by the application of a Kalman filter, a powerful algorithm to estimate the state of a linear dynamic system from noisy measurements. We show that the optimal Kalman filter parameters can be determined in an appropriate experimental setting, and that the Kalman filter can markedly reduce the positioning error while retaining the intrinsic fluctuations of the dynamic process. We believe the Kalman filter can potentially serve as a powerful tool to infer a trajectory of ultra-high fidelity from noisy images, revealing the details of dynamic cellular processes.

A general method for improving spatial resolution by optimization of electron multiplication in CCD imaging.

The electron-multiplying charge-coupled device (EMCCD) camera possesses an electron multiplying function that can effectively convert the weak incident photon signal to amplified electron output, thereby greatly enhancing the contrast of the acquired images. This device has become a popular photon detector in single-cell biophysical assays to enhance subcellular images. However, the quantitative relationship between the resolution in such measurements and the electron multiplication setting in the EMCCD camera is not well-understood. We therefore developed a method to characterize the exact dependence of the signal-to-noise-ratio (SNR) on EM gain settings over a full range of incident light intensity. This information was further used to evaluate the EMCCD performance in subcellular particle tracking. We conclude that there are optimal EM gain settings for achieving the best SNR and the best spatial resolution in these experiments. If it is not used optimally, electron multiplication can decrease the SNR and increases spatial error.

A novel approach to high accuracy of video-based microrheology.

Video-based particle tracking monitors the microscopic movement of labeled biomolecules and fluorescent probes within a complex cellular environment. Information gained from this technique enables us to extract the dynamic behavior of biomolecules and the local mechanical properties inside the cell from a tracked particle's mean-square displacement (MSD). However, MSD measurements are highly susceptible to static error introduced by noise in the image acquisition process that leads to an incorrect positioning of the particle. Static error can mask the subtle effects from the local microenvironment on the MSD and potentially generate misleading conclusions about the biophysical properties of cells. An approach that greatly increases the accuracy of MSD measurements is presented herein by combining experimental data with Monte Carlo simulations to eliminate the inherent static error. This practical method of static error correction greatly advances particle-tracking techniques.

The relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy: A systematic review and a meta-analysis.

BACKGROUND: Vitamin D is a fat-soluble vitamin that is related to the health of the human body and is an indispensable nutrient for human beings. Some studies indicated that type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) may be associated with vitamin D deficiency, but the current understanding of this point of view remains controversial. This study aimed to evaluate the correlation between serum 25-hydroxyl vitamin D (25 [OH] D) concentration and DPN in patients with T2DM by a meta-analysis, and to provide a reference for doctors. METHODS: Relevant studies were selected from the PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP databases, and Wanfang Data Knowledge Service Platform databases dating from 2000 to December 2017. A total of 75 articles related to serum 25 (OH) D and DPN were selected from 2000 to December 2017. Based on the inclusion and exclusion criteria of the literature, a quality assessment was conducted using the Newcastle-Ottawa scale, and a meta-analysis was performed by RevMan5.3 statistical software. RESULTS: Thirteen studies that involved a total of 2814 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis results, heterogeneity test showed that, P < .000 01, I = 92%, calculation by random effect model revealed that, the serum concentration of 25 (OH) D in T2DM combined with DPN group was lower than that in the group without DPN (weighted mean difference = -0.74, 95% confidence interval: -1.03 to -0.46) CONCLUSIONS:: Vitamin D is associated with type 2 DPN (DPN), and vitamin D deficiency can lead to an increased risk of type 2 DPN. However, more high-quality research is needed.

Clinical Effect of Intravenous Vitamin C on Viral Myocarditis in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To comprehensively compare the effects of conventional therapy combined with intravenous vitamin C and conventional therapy on viral myocarditis in children through a meta-analysis. METHODS: Relevant articles including clinical trials of normal treatment combined with intravenous vitamin C and conventional therapy for viral myocarditis in children that were published between January 2000 and February 2018 were selected from PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and WANFANG database. The quality of the included studies was assessed using the Cochrane systematic review method (version 5.1.0); data quality was evaluated by two independent researchers. The total effective rate; LDH, CK, and CK-MB levels; and other indicators were analyzed using Rev Man 5.3 software. RESULTS: Eight studies were eligible for this meta-analysis, which included a total of 426 patients in the treatment group and 363 patients in the control group. The meta-analysis results of six studies showed that the total effective rate of intravenous vitamin C combined with conventional therapy was higher than that of conventional therapy alone [Z = 5.46, 95% confidence interval (CI): 1.21 (1.13 to 1.30), P < 0.00001]; that of five studies showed that LDH levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 3.70, 95% CI: -1.88 (-2.88 to -0.88), P = 0.0002]; that of three studies showed that CK levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 4.21, 95% CI: -0.55 (-0.81 to -0.30), P < 0.0001]; that of four studies showed that CK-MB levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 13.64, 95% CI: -1.44 (-1.65 to -1.24), P < 0.00001]; that of two studies showed that CD3 levels were higher in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 2.45, 95% CI: 0.41 (0.08-0.73), P = 0.01]; that of two studies showed no significant difference in changes in CD4 levels between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.28, 95% CI: -0.21 (-1.69 to 1.28), P = 0.78]; and that of two studies showed no significant difference in changes in CD4/CD8 between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.07, 95% CI: -0.03 (-0.73 to 0.67), P = 0.94]. CONCLUSION: The meta-analysis results showed that intravenous vitamin C combined with conventional therapy is better than the simple, conventional therapy for the treatment of viral myocarditis in children in terms of the total effective rate and LDH, CK, and CK-MB levels.

Intracellular mechanics of migrating fibroblasts.

Cell migration is a highly coordinated process that occurs through the translation of biochemical signals into specific biomechanical events. The biochemical and structural properties of the proteins involved in cell motility, as well as their subcellular localization, have been studied extensively. However, how these proteins work in concert to generate the mechanical properties required to produce global motility is not well understood. Using intracellular microrheology and a fibroblast scratch-wound assay, we show that cytoskeleton reorganization produced by motility results in mechanical stiffening of both the leading lamella and the perinuclear region of motile cells. This effect is significantly more pronounced in the leading edge, suggesting that the mechanical properties of migrating fibroblasts are spatially coordinated. Disruption of the microtubule network by nocodazole treatment results in the arrest of cell migration and a loss of subcellular mechanical polarization; however, the overall mechanical properties of the cell remain mostly unchanged. Furthermore, we find that activation of Rac and Cdc42 in quiescent fibroblasts elicits mechanical behavior similar to that of migrating cells. We conclude that a polarized mechanics of the cytoskeleton is essential for directed cell migration and is coordinated through microtubules.

Cdc42 mediates nucleus movement and MTOC polarization in Swiss 3T3 fibroblasts under mechanical shear stress.

Nucleus movement is essential during nucleus positioning for tissue growth and development in eukaryotic cells. However, molecular regulators of nucleus movement in interphase fibroblasts have yet to be identified. Here, we report that nuclei of Swiss 3T3 fibroblasts undergo enhanced movement when subjected to shear flows. Such movement includes both rotation and translocation and is dependent on microtubule, not F-actin, structure. Through inactivation of Rho GTPases, well-known mediators of cytoskeleton reorganization, we demonstrate that Cdc42, not RhoA or Rac1, controls the extent of nucleus translocation, and more importantly, of nucleus rotation in the cytoplasm. In addition to generating nuclei movement, we find that shear flows also causes repositioning of the MTOC in the direction of flow. This behavior is also controlled by Cdc42 via the Par6/protein kinase Czeta pathway. These results are the first to establish Cdc42 as a molecular regulator of not only shear-induced MTOC polarization in Swiss 3T3 fibroblasts, but also of shear-induced microtubule-dependent nucleus movement. We propose that the movements of MTOC and nucleus are coupled chemically, because they are both regulated by Cdc42 and dependent on microtubule structure, and physically, possibly via Hook/SUN family homologues similar to those found in Caenorhabditis elegans.

Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns.

Various subcellular activities, such as protrusion and detachment, compose a cell migration process. The molecular mechanisms of these subcellular activities have been elucidated. However, there is no method that can assess the contributions of these subcellular activities to the global cell migration pattern of a given cell type. Hence, we develop a powerful approach based on CN correlations that quantitatively profiles the cell migration pattern of a given cell type in terms of assembled subcellular activities. In this way, we bridge migration data at the cellular level with underlying molecular mechanisms. The CN correlation profile is found to uniquely and consistently represent the cell migration pattern of each cell type probed. It can clearly reveal the effects of molecular perturbations, such as Y27632 and Cdc42 knockdown on each subcellular migratory activity. As a result, the CN correlation approach serves as a cell dynamic descriptor that can extract comprehensive quantitative data from cell migration movies for integrative biological analyses.

Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials.

AIM: To investigate whether vitamin C is effective in the treatment of the common cold. METHOD: After systematically searching the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and WANFANG databases, 9 randomized placebo-controlled trials were included in our meta-analysis in RevMan 5.3 software, all of which were in English. RESULTS: In the evaluation of vitamin C, administration of extra therapeutic doses at the onset of cold despite routine supplementation was found to help reduce its duration (mean difference (MD) = -0.56, 95% confidence interval (CI) [-1.03, -0.10], and P = 0.02), shorten the time of confinement indoors (MD = -0.41, 95% CI [-0.62, -0.19], and P = 0.0002), and relieve the symptoms associated with it, including chest pain (MD = -0.40, 95% CI [-0.77, -0.03], and P = 0.03), fever (MD = -0.45, 95% CI [-0.78, -0.11], and P = 0.009), and chills (MD = -0.36, 95% CI [-0.65, -0.07], and P = 0.01). CONCLUSIONS: Extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements.

Penetrating living cells using semiconductor nanowires.

A recent publication by Kim et al. on penetrating both human embryonic kidney cells and mouse embryonic stem cells with Si nanowires highlights the increasing interest in using proven semiconductor materials not only to detect specific biomolecules in solutions but also to deliver genetic material or potentially screen for the presence of particular molecules at the cell level. Many semiconductors are biocompatible and this recent work has shown that penetrating cells with large diameters compared with those of the semiconductor nanowire is not fatal to the cell and that the cells remain functional for a few days.

Rho kinase regulates the intracellular micromechanical response of adherent cells to rho activation.

Local sol-gel transitions of the cytoskeleton modulate cell shape changes, which are required for essential cellular functions, including motility and adhesion. In vitro studies using purified cytoskeletal proteins have suggested molecular mechanisms of regulation of cytoskeleton mechanics; however, the mechanical behavior of living cells and the signaling pathways by which it is regulated remains largely unknown. To address this issue, we used a nanoscale sensing method, intracellular microrheology, to examine the mechanical response of the cell to activation of the small GTPase Rho. We observe that the cytoplasmic stiffness and viscosity of serum-starved Swiss 3T3 cells transiently and locally enhances upon treatment with lysophosphatidic acid, and this mechanical behavior follows a trend similar to Rho activity. Furthermore, the time-dependent activation of Rho decreases the degree of microheterogeneity of the cytoplasm. Our results reveal fundamental differences between intracellular elasticity and cellular tension and suggest a critical role for Rho kinase in the regulation of intracellular mechanics.

Efficacy and safety of the "Xingnao Kaiqiao" acupuncture technique via intradermal needling to treat postoperative gastrointestinal dysfunction of laparoscopic surgery: study protocol for a randomized controlled trial.

BACKGROUND: Xingnao Kaiqiao acupuncture involves needling of the Neiguan (PC6), Renzhong (DU26), and Sanyinjiao (SP6) acupoints. The technique has a significant clinical effect in many neurological diseases. In the present report, we have developed a protocol for a scientific trial to analyze whether Xingnao Kaiqiao can be used to treat gastrointestinal dysfunction after laparoscopic surgery. In this context, we intend to execute a double-blind, randomized controlled trial to assess the efficacy and safety of Xingnao Kaiqiao acupuncture via intradermal needling. METHODS/DESIGN: This will be a single-center, double-blind, randomized controlled clinical trial. It has been designed on the basis of the Consolidated Standards of Reporting Trials (CONSORT 2010) guidelines and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). The subjects will be recruited from among inpatients scheduled for laparoscopic surgery at the Department of Minimally Invasive Surgery, Tianjin Nankai Hospital, Tianjin, China. Using random numbers generated in SPSS 19.0, the recruited subjects will be allocated to either the "Xingnao Kaiqiao" group or the sham stimulation group. A specially appointed investigator will be in charge of the randomization. Xingnao Kaiqiao via intradermal needling (or sham needling) will be administered 6 h after laparoscopic surgery, and then every 12 h for a total of six sessions, each of which will last 3 min. The subjects will undergo their first evaluation shortly before the first treatment (6 h after laparoscopic surgery); evaluations will be repeated every 12 h until a total of seven evaluations have been completed. The primary outcome will be the time until the first postoperative flatus. The secondary outcomes will be: the time until the first postoperative defecation; levels of abdominal pain, abdominal distension, and nausea; blood ghrelin level; occurrence of vomiting; psychological status; and quality of life. DISCUSSION: This upcoming randomized clinical trial was designed as a standardized method to assess the efficacy and safety of Xingnao Kaiqiao acupuncture using intradermal needles on PC6, DU26, and SP6 in the treatment of gastrointestinal dysfunction after laparoscopic surgery. We aim to provide evidence and thus improve the clinical application of this technique. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-17010763 . Registered on 2 March 2017.

Structure of the actin crosslinking core of fimbrin.

Filamentous actin is organized into bundles and orthogonal networks by the fimbrin/alpha-actinin superfamily of F-actin crosslinking proteins. The crystal structure of the Arabidopsis thaliana and Schizosaccharomyces pombe fimbrin cores provides the first description of a functional F-actin crosslinking protein and highlights the compact and distinctly asymmetric organization of the fimbrin molecule, in which the two actin binding domains present distinct surfaces to solvent. The mapping of functionally important residues onto the structure affords new insights into the binding process and provides additional constraints which must be accommodated by models for F-actin binding and crosslinking. Most strikingly, this work provides unique insight into the mechanistic features of conditional-lethal mutants and their extragenic suppressors, which highlight conformational and dynamic properties required for fimbrin function. These results underscore the power of jointly considering structural and genetic suppressor data for obtaining unexpected and biologically relevant mechanistic information.

Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis.

Cell migration is an essential process in organism development and physiological maintenance. Although current methods permit accurate comparisons of the effects of molecular manipulations and drug applications on cell motility, effects of alterations in subcellular activities on motility cannot be fully elucidated from those methods. Here, we develop a strategy termed cell-nuclear (CN) correlation to parameterize represented dynamic subcellular activities and to quantify their contributions in mesenchymal-like migration. Based on the biophysical meaning of the CN correlation, we propose a cell migration potential index (CMPI) to measure cell motility. When the effectiveness of CMPI was evaluated with respect to one of the most popular cell migration analysis methods, Persistent Random Walk, we found that the cell motility estimates among six cell lines used in this study were highly consistent between these two approaches. Further evaluations indicated that CMPI can be determined using a shorter time period and smaller cell sample size, and it possesses excellent reliability and applicability, even in the presence of a wide range of noise, as might be generated from individual imaging acquisition systems. The novel approach outlined here introduces a robust strategy through an analysis of subcellular locomotion activities for single cell migration assessment.

Effect of length, topology, and concentration on the microviscosity and microheterogeneity of DNA solutions.

The viscoelastic behavior of chromosomal DNA, which is heterogeneously distributed within the nucleus, may influence the diffusion of nuclear organelles and proteins. To identify some of the parameters that affect DNA viscoelasticity, we use the high-throughput method of multiple-particle nanotracking to measure the microviscosity and degree of heterogeneity of solutions of chromosomal DNA, linear DNA, and circular double-stranded DNA over a wide range of concentrations and lengths. The thermally excited displacements of multiple fluorescent microspheres imbedded in DNA solutions are monitored with 5nm spatial resolution and 30Hz temporal resolution, from which mean-squared displacement (MSD) and viscosity distributions are generated. For all probed DNA solutions but the most concentrated solution of the longest molecules, the ensemble-averaged MSD increases linearly with time at all probed time scales, a signature of viscous transport. The associated mean viscosity of the DNA solutions increases slowly with concentration for circular DNA and more rapidly for linear DNA, but more slowly than predicted by theory. The heterogeneity of the DNA solutions is assessed by computing the relative contributions of the 10%, 25%, and 50% highest values of MSD and viscosity to the ensemble-averaged MSD and viscosity. For both linear DNA and circular DNA, these contributions are much larger than observed in homogeneous liquids such as glycerol. The microheterogeneity of the linear DNA solutions increases with concentration more significantly for linear DNA than circular DNA. These in vitro results suggest that the topology, local concentration, and length of DNA influence the microrheology and microheterogeneity of the DNA within the nucleus.