Pregnancy is a physiological process with pronounced hormonal fluctuations in females, and relatively little is known regarding how pregnancy influences the ecological shifts of supragingival microbiota. In this study, supragingival plaques and salivary hormones were collected from 11 pregnant women during pregnancy (P1, ≤14 weeks; P2, 20–25 weeks; P3, 33–37 weeks) and the postpartum period (P4, 6 weeks after childbirth). Seven non-pregnant volunteers were sampled at the same time intervals. The microbial genetic repertoire was obtained by 16S rDNA sequencing. Our results indicated that the Shannon diversity in P3 was significantly higher than in the non-pregnant group. The principal coordinates analysis showed distinct clustering according to gestational status, and the partial least squares discriminant analysis identified 33 genera that may contribute to this difference. There were differentially distributed genera, among which Neisseria, Porphyromonas, and Treponema were over-represented in the pregnant group, while Streptococcus and Veillonella were more abundant in the non-pregnant group. In addition, 53 operational taxonomic units were observed to have positive correlations with sex hormones in a redundancy analysis, with Prevotella spp. and Treponema spp. being most abundant. The ecological events suggest that pregnancy has a role in shaping an at-risk-for-harm microbiota and provide a basis for etiological studies of pregnancy-associated oral dysbiosis.

BackgroundA new mechanism for intercellular communication has recently emerged that involves intercellular transfer of extracellular vesicles (EVs). Several studies have indicated that EVs may play a potential role in cell‐to‐cell communication between macrophage foam cells and vascular smooth muscle cells (VSMCs) in atherosclerotic lesion.Methods and ResultsThis study involved the comparison of circulating EVs from atherosclerotic patients and control participants. The results showed that the circulation of the patients contained more leukocyte‐derived EVs and that these EVs promoted more VSMC adhesion and migration than those of healthy participants. We then established a macrophage foam cell model and characterized the EVs from the macrophages. We used flow cytometric analyses and cell migration and adhesion assays and determined that the foam cells generated more EVs than the normal macrophages and that the foam cell–derived EVs were capable of promoting increased levels of VSMC migration and adhesion. Furthermore, we performed a proteomic analysis of the EVs. The data showed that the foam cell–derived EVs may promote VSMC adhesion and migration by regulating the actin cytoskeleton and focal adhesion pathways. In addition, Western blotting revealed that foam cell–derived EVs could promote the phosphorylation of ERK and Akt in VSMCs in a time‐dependent manner. We also found that foam cell–derived EVs could enter the VSMCs and transfer integrins to the surface of these cells.ConclusionsThe data in our present study provide the first evidence that EVs from foam cells could promote VSMC migration and adhesion, which may be mediated by the integration of EVs into VSMCs and the subsequent downstream activation of ERK and Akt.

Minimally invasive endodontics emphasizes preservation of a maximal amount of healthy tooth tissue. However, whether the tooth structure preserved by minimally invasive endodontics can maintain higher fracture resistance is unclear. This study aimed to compare the biomechanics on teeth after minimally invasive (MI) preparation and straight-line (SL) preparation using finite element analysis. Six finite element analysis models of a mandibular first molar were constructed and divided into two groups (MI and SL). Two loads of 250 N, one vertically stimulating the vertical masticatory force and the other given 45° to the longitudinal axis of the tooth, were applied. Stresses in the teeth were calculated and analyzed. Under both vertical and 45° loads, the greatest stresses were located at the margin of the cavities on the occlusal surfaces. The stress concentration areas of teeth with minimally invasive access cavities were smaller than those of teeth prepared with straight-line opening in coronal and cervical areas. The stress concentration points in the cervical areas increased with the increase of canal taper in the coronal third. Minimally invasive access preparation reduced the stress distribution in crown and cervical regions. A smaller taper cervical enlargement caused lower stress in the cervical region.

Bone tissue engineering is an area of regenerative medicine that attempts to repair bone defects. Seed cells such as dental pulp stem cells (DPSCs) and adipose tissue-derived stem cells (ADSCs) are two of the most well-characterized cells for bone regeneration because their use involves few ethical constraints and they have the ability to differentiate into multiple cell types, secreting growth factors and depositing mineral. However, bone regeneration ability of these cells remains unclear. This study aimed to compare the bone formation capacity of DPSCs and ADSCs in vitro and in vivo. Studies revealed that DPSCs had enhanced colony-forming ability, higher proliferative ability, stronger migration ability and higher expression of angiogenesis-related genes. They also secreted more vascular endothelial growth factor compared to ADSCs. In contrast, ADSCs grew more slowly compared to DPSCs but exhibited greater osteogenic differentiation potential, higher expression of osteoblast marker genes, and greater mineral deposition. Furthermore, after DPSCs and ADSCs were implanted into a mandibular defect of a rat for 6 weeks, ADSCs showed visible bone tissue as early as week 1 and promoted faster and greater bone regeneration compared to the DPSC group. These results suggest that ADSCs might be more useful than DPSCs for bone regeneration.

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BackgroundRecent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD.MethodsWe tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition.ResultsAt stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested.ConclusionsOur results provide direct evidence that tremor in the upper extremity of patients with PD can be inhibited to a large extent with evoked cutaneous reflexes via surface stimulation of the dorsal hand skin area innervated by the superficial radial nerve.

BackgroundDysfunctional high-density lipoprotein (HDL) may have pro-inflammatory effects on the endothelial cells,which causes atherosclerosis in type 2 diabetes mellitus (T2DM). HDL is a major carrier of sphingosine-1-phosphate (S1P) in plasma while S1P exhibits multiple biological activities. However, potential role of HDL and S1P in T2DM remains unexplored. We hypothesized that diabetic HDL with higher contents of S1P exerts beneficial effects on the vascular system.MethodsSubjects with T2DM with or without proved large arteries atherosclerosis and normal controls (n=15 for each group) were recruited in the present study. HDL was isolated from the subjects by ultracentrifugation. The levels of HDL-associated S1P were determined by UPLC-MS/MS. The protective function of diabetic HDL and S1P was evaluated by measuring cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release by human umbilical vein endothelial cells (HUVECs) using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.ResultsThe S1P levels in isolated HDL were significantly increased in T2DM subjects compared with controls (235.6 ± 13.4 vs 195.0 ± 6.4 ng/mg, P< 0.05). The diabetic HDL exerted greater protective effects on inducing COX-2 expression and PGI-2 release by HUVECs than those of control HDL (p < 0.05, p < 0.01, respectively). Pertussis toxin, a common inhibitor of G-couple protein receptors, and VPC 23019, an antagonist of S1P receptor 1 and 3 significantly attenuated HDL-induced COX-2 expression and PGI-2 release.ConclusionsDiabetic HDL carries higher level of S1P compared with normal HDL, which has the potential to contribute to protective effects on endothelial cells by inducing COX-2 expression and PGI-2 release. These findings provide a new insight of S1P function in T2DM patients, possibly leading to a new therapeutic target.

Objective One goal of neuromorphic engineering is to create “realistic” robotic systems that interact with the physical world by adopting neuromechanical principles from biology. Critical to this is the methodology to implement the spinal circuitry responsible for the behavior of afferented muscles. At its core, muscle afferentation is the closed-loop behavior arising from the interactions among populations of muscle spindle afferents, alpha and gamma motoneurons, and muscle fibers to enable useful behaviors. Approach We used programmable Very-Large-Scale-Circuit (VLSI) hardware to implement simple models of spiking neurons, skeletal muscles, muscle spindle proprioceptors, alpha-motoneuron recruitment, gamma motoneuron control of spindle sensitivity, and the monosynaptic circuitry connecting them. This multi-scale system of populations of spiking neurons emulated the physiological properties of a pair of antagonistic afferented mammalian muscles (each simulated by 1,024 alpha- and gamma-motoneurones) acting on a joint via long tendons. Main results This integrated system was able to maintain a joint angle, and reproduced stretch reflex responses even when driving the nonlinear biomechanics of an actual cadaveric finger. Moreover, this system allowed us to explore numerous values and combinations of gamma-static and gamma-dynamic gains when driving a robotic finger, some of which replicated some human pathological conditions. Lastly, we explored the behavioral consequences of adopting three alternative models of isometric muscle force production. We found that the dynamic responses to rate-coded spike trains produce force ramps that can be very sensitive to tendon elasticity, especially at high force output. Significance Our methodology produced, to our knowledge, the first example of an autonomous, multi-scale, neuromorphic, neuromechanical system capable of creating realistic reflex behavior in cadaveric fingers. This research platform allows us to explore the mechanisms behind healthy and pathological sensorimotor function in the physical world by building them from first principles, and it is a precursor to neuromorphic robotic systems.