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Summary: With the commercialization of the electric vehicles, the large‐scale lithium‐ion cells as the power of electric vehicles are to be retired. The second‐use of retired cells is of great significance to improve the battery economy. A fast classification and regroup evaluation method of the retired lithium‐ion cells are proposed in this paper to improve the classification efficiency of retired lithium‐ion cells and adapt to the regroup under different conditions. The lithium‐ion cells after being balanced in parallel are charged in series with a constant current. A support vector regression (SVR) model with the parameters optimized by the particle swarm optimization (PSO) algorithm is built for the fast capacity estimation and the error will not exceed 0.3%. Different cells regrouped means different performance. In order to improve the consistency of retired cells and satisfy different using conditions, a Weighted‐K‐means algorithm is proposed in this paper to regroup the cells with the known capacity and internal resistance. The classification method is evaluated by the voltage consistency of cells using different working conditions, which indicates capacity occupied a large proportion can meet the requirement of energy condition meanwhile keep a good consistency. But the resistance will dominate in algorithm under conditions which have requirement for instantaneous power. [ABSTRACT FROM AUTHOR]

Summary: In situ growing conductive polyaniline (PANi) has been regarded as a functional binder to enhance the performance of silicon based anodes in half cells, while few papers discussing the influence of Mn2+ from cathode on full cells. In this paper, the effects of Mn2+ on NSi@PANi electrodes in both half and full cells are investigated, and the mechanism for the fast capacity fade of LiMn2O4/NSi@PANi full cell is elucidated. Results reveal that the full cell will significant accelerate the capacity fade of NSi@PANi anode, and the extra consumption of active Li+ and electrolytes caused by the deposited Mn2+ on silicon anodes in lithium manganate (LMO)/NSi@PANi full cells is confirmed as the main reason of the capacity fade and lower coulombic efficiency for the excessive growth of solid electrolyte interphase. [ABSTRACT FROM AUTHOR]

Grid cells and place cells are important neurons in the animal brain. The information transmission between them provides the basis for the spatial representation and navigation of animals and also provides reference for the research on the autonomous navigation mechanism of intelligent agents. Grid cells are important information source of place cells. The supervised learning and unsupervised learning models can be used to simulate the generation of place cells from grid cell inputs. However, the existing models preset the firing characteristics of grid cell. In this paper, we propose a united generation model of grid cells and place cells. First, the visual place cells with nonuniform distribution generate the visual grid cells with regional firing field through feedforward network. Second, the visual grid cells and the self-motion information generate the united grid cells whose firing fields extend to the whole space through genetic algorithm. Finally, the visual place cells and the united grid cells generate the united place cells with uniform distribution through supervised fuzzy adaptive resonance theory (ART) network. Simulation results show that this model has stronger environmental adaptability and can provide reference for the research on spatial representation model and brain-inspired navigation mechanism of intelligent agents under the condition of nonuniform environmental information. [ABSTRACT FROM AUTHOR]

The contribution of this present paper is to propose a method that combines a chemical Brusselator reaction-diffusion system with a biological cell system via gap junction for controlling and visualizing the frequency and magnitude of chaotic intracellular calcium oscillations in two cell types, including nonexcitable cells and the glial cells. This produces a wide variety of oscillatory behaviors similar to those reported in numerous biological experiments. We particularly show that in the majority of chaos cases, the reactor to cell coupling can induce the generation of regular calcium oscillations as the coupling strength is varied. Together with the proposed method of coupled models, the regularity of these chaotic oscillations enables us to gain better understanding and extensive insights into the overall coupling dynamics. [ABSTRACT FROM AUTHOR]

Densely deploying small cells will be a solution to provide explosive data requirements in fifth-generation networks. Because users often cluster together in popular locations of an urban area, congested small cells in the popular sites are also gathered. Traditional load balancing schemes generally only consider neighboring cells when offloading users are not suitable for clusters of overloaded cells. This paper considers groups of overloaded cells in the load balancing problem. The objective is to maximize the quality-of-service satisfaction ratio. To solve the problem, we propose a multidepth offloading algorithm with the consideration of the radio resource allocation. The proposed multidepth offloading algorithm can be applied no matter that congested small cells are gathered or not. Compared with a previous offloading algorithm and a baseline, the simulation results show that our proposed algorithm can increase 16% QoS satisfaction ratio in a real user distribution and 13% QoS satisfaction ratio in a clustered user placement. [ABSTRACT FROM AUTHOR]

Small cells are expected to increase the capacity and the coverage of a wireless network. Since the transmission ranges of the small cells overlap with each other, a user equipment (UE) can be located within the service areas of multiple cells. Therefore, the association decisions made by the small cells and the UEs influence the energy efficiency of the cells and the data rates provided to the UEs. However, if they attempt to achieve their goals selfishly, the network may become instable in that a UE has to change its associated cell and a cell has to change the set of UEs associated with it frequently. To tackle the problem, in this paper, we propose an association game between UEs and cells. We cast the problem as a matching game where each player has preference over the other player. Then, we propose an association algorithm composed of a UE-side part and a cell-side part. Through simulation studies, we show that the proposed method outperforms the other methods in that it can enhance the average energy efficiency of the small cell network and the data rates that UEs can obtain from the network. [ABSTRACT FROM AUTHOR]

This paper presents a novel ultracompact narrow bandpass filter with high selectivity. The proposed filter is composed of cascading two basic cells. Each cell is basically a microstrip line loaded with a quasiplanar resonator and series gaps which can be fabricated using a standard multilayer printed circuit board technology. The structure is analyzed through an equivalent circuit and full-wave simulations. The simulation results are compared with experimental measurements demonstrating a good agreement between them. The measurement indicates that the realized bandpass filter at the center frequency of 1 GHz has a fractional bandwidth of 2.2%. Most importantly, in comparison with other similar recent works, it is shown that the proposed filter has the smallest size. [ABSTRACT FROM AUTHOR]

Electrical detection of biotic materials and their properties is always crucial in Biomedical Engineering. It emphasizes elaborate analysis of a certain disease diagnosis using electrical means which includes the study of electrical properties followed by detection, identification, and quantification of biotic entities. Proper and early detection of cells, which can be normal or cancerous, holds never-ending demand. This review emphasizes the electrical characterization methods in modeling and classification of cell properties. Moreover, standard methods have been highlighted and discussed to yield performance analysis. This study suggests that techniques presented for single-cell analysis (SCA) are always precise and hold great scope compared to those for cell mixture. SCA plays a promising role in disease diagnosis and treatment planning, as it not only detects the cells but also helps in identification. Distinct electrical-based cell detection techniques are highlighted, along with the pros and cons of various SCA devices. The content, in terms of methodologies and available techniques, of this review paper is useful to attract researchers working in this area. [ABSTRACT FROM AUTHOR]

Primary cutaneous anaplastic large cell lymphoma is a CD-30 positive lymphoproliferative disorder with good prognosis, usually treated with radiation therapy and surgery. Head, neck, and extremities are the most frequently involved sites. In this paper, we describe an unusual case of oral localization, recurring after skin-involving radiotherapy, successfully treated with sixteen cycles of brentuximab vedotin. This could be a more effective approach with a less detrimental toll for treating these rare disorders. [ABSTRACT FROM AUTHOR]

In this paper, a delayed viral dynamical model that considers two different transmission methods of the virus and apoptosis of bystander cells is proposed and investigated. The basic reproductive number R 0 of the model is derived. Based on the basic reproductive number, we prove that the disease-free equilibrium E 0 is globally asymptotically stable for R 0 < 1 by constructing suitable Lyapunov functional. For R 0 > 1 , by regarding the time delay as bifurcation parameter, the existence of local Hopf bifurcation is investigated. The results show that time delay can change the stability of endemic equilibrium and cause periodic oscillations. Finally, we give some numerical simulations to illustrate the theoretical findings. [ABSTRACT FROM AUTHOR]

Biological and engineering studies of Hess-Murray’s law are focused on assemblies of tubes with impermeable walls. Blood vessels and airways have permeable walls to allow the exchange of fluid and other dissolved substances with tissues. Should Hess-Murray’s law hold for bifurcating systems in which the walls of the vessels are permeable to fluid? This paper investigates the fluid flow in a porous-walled T-shaped assembly of vessels. Fluid flow in this branching flow structure is studied numerically to predict the configuration that provides greater access to the flow. Our findings indicate, among other results, that an asymmetric flow (i.e., breaking the symmetry of the flow distribution) may occur in this symmetrical dichotomous system. To derive expressions for the optimum branching sizes, the hydraulic resistance of the branched system is computed. Here we show the T-shaped assembly of vessels is only conforming to Hess-Murray’s law optimum as long as they have impervious walls. Findings also indicate that the optimum relationship between the sizes of parent and daughter tubes depends on the wall permeability of the assembled tubes. Our results agree with analytical results obtained from a variety of sources and provide new insights into the dynamics within the assembly of vessels. [ABSTRACT FROM AUTHOR]

Timothy is a novel large scale modelling framework that allows simulating of biological processes involving different cellular colonies growing and interacting with variable environment. Timothy was designed for execution on massively parallel High Performance Computing (HPC) systems. The high parallel scalability of the implementation allows for simulations of up to 109 individual cells (i.e., simulations at tissue spatial scales of up to 1 cm3 in size). With the recent advancements of the Timothy model, it has become critical to ensure appropriate performance level on emerging HPC architectures. For instance, the introduction of blood vessels supplying nutrients to the tissue is a very important step towards realistic simulations of complex biological processes, but it greatly increased the computational complexity of the model. In this paper, we describe the process of modernization of the application in order to achieve high computational performance on HPC hybrid systems based on modern Intel® MIC architecture. Experimental results on the Intel Xeon Phi™ coprocessor x100 and the Intel Xeon Phi processor x200 are presented. [ABSTRACT FROM AUTHOR]

This paper investigates the protective effect of interleukin-1 receptor antagonist (IL-1Ra) released from hyaluronic acid chitosan (HA-CS) microspheres in a controlled manner on IL-1β-induced inflammation and apoptosis in chondrocytes. The IL-1Ra release kinetics was characterized by an initial burst release, which was reduced to a linear release over eight days. Chondrocytes were stimulated with 10 ng/ml IL-1β and subsequently incubated with HA-CS-IL-1Ra microspheres. The cell viability was decreased by IL-1β, which was attenuated by HA-CS-IL-1Ra microspheres as indicated by an MTT assay. ELISA showed that HA-CS-IL-1Ra microspheres inhibited IL-1β-induced inflammation by attenuating increases in NO2- and prostaglandin E2 levels as well as increase in glycosaminoglycan release. A terminal deoxyribonucleotide transferase deoxyuridine triphosphate nick-end labeling assay revealed that the IL-1β-induced chondrocyte apoptosis was decreased by HA-CS-IL-1Ra microspheres. Moreover, HA-CS-IL-1Ra microspheres blocked IL-1β-induced chondrocyte apoptosis by increasing B-cell lymphoma 2 (Bcl-2) and decreasing Bcl-2-associated X protein and caspase-3 expressions at mRNA and protein levels, as indicated by reverse-transcription quantitative polymerase chain reaction and western blot analysis, respectively. The results of the present study indicated that HA-CS-IL-1Ra microspheres as a controlled release system of IL-1Ra possess potential anti-inflammatory and antiapoptotic properties in rat chondrocytes due to their ability to regulate inflammatory factors and apoptosis associated genes. [ABSTRACT FROM AUTHOR]

Owing to the abuse of antibiotics, drug resistance of pathogenic bacteria becomes more and more serious. Therefore, it is interesting to develop a more reasonable way to solve this issue. Because they can destroy the bacterial cell structure and then kill the infectious bacterium, the bacterial cell wall lyases are suitable candidates of antibacteria sources. Thus, it is urgent to develop an accurate and efficient computational method to predict the lyases. Based on the consideration, in this paper, a set of objective and rigorous data was collected by searching through the Universal Protein Resource (the UniProt database), whereafter a feature selection technique based on the analysis of variance (ANOVA) was used to acquire optimal feature subset. Finally, the support vector machine (SVM) was used to perform prediction. The jackknife cross-validated results showed that the optimal average accuracy of 84.82% was achieved with the sensitivity of 76.47% and the specificity of 93.16%. For the convenience of other scholars, we built a free online server called Lypred. We believe that Lypred will become a practical tool for the research of cell wall lyases and development of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Lichens are a life form in which algae and fungi have a symbiotic relationship and have various biological activities, including anti-inflammatory and antiproliferative activities. This is the first study to investigate the anti-inflammatory activity of a Phlebia sp. fungal extract (PSE) isolated from Peltigera neopolydactyla in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage. PSE reduced the production of the proinflammatory cytokine (tumor necrosis factor-α, interleukin-6, and interleukin-1β), chemokine (granulocyte-macrophage colony-stimulating factor), nitric oxide, and prostaglandin E2 in the LPS-stimulated RAW264.7 macrophages. Especially, PSE inhibits the phosphorylation of activator protein-1 (AP-1) signaling (c-Fos and c-Jun) and their upstream mitogen-activated protein kinase kinases/mitogen-activated protein kinases (MKK/MAPKs: MKK4, MKK7, and JNK) and finally reduced the production of the inflammatory cytokines. The inhibitory effects mainly act via suppressing JNK-mediated AP-1 rather than the NF-κB pathway. Furthermore, PSE inhibited the production of final inflammatory effector molecules involved in AP-1 signaling, including nitric oxide (NO) and prostaglandin E2 (PGE2). Here, we report that PSE has the potential to be developed as an anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial intima. As AS represents the most common type of vascular disease, it affects millions of individuals and is a source of high morbidity and mortality rates worldwide. Overwhelming evidence indicates that AS-related inflammation is mediated by proinflammatory cytokines, chemokines, adhesion molecules and inflammatory signaling pathways, with each of these factors being shown to play critical roles during the entire progression of AS. While a number of drugs have been approved for use in the treatment of AS, their benefits are modest, which underscores the urgency for the development of new drug therapies. In part, these deficits in effective drugs can be attributable to the lack of a clear understanding of the molecular mechanisms of AS. In this study, we investigate the capacity for thrombin to trigger inflammation and induce cell proliferation in vascular smooth muscle cells (VSMCs). We then assessed the effects of baicalin and its potential mechanisms on VSMC inflammation as induced by thrombin. Baicalin, which is a natural bioactive compound of S. baicalensis Georgi (SBG), exerted a protective effect against thrombin-induced VSMC inflammation as resulting from the upregulation of PAR-1. This protection as exerted by baicalin appears to reside in its capacity to produce an inhibitory effect on the thrombin-induced activation of the ERK1/2 pathway. These findings suggest that baicalin may be a promising candidate for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background. Subclinical mastitis is one of the most common reproductive diseases in dairy cows. Qicao Rukang powder is a Chinese herbal compound mixture developed to treat subclinical mastitis in dairy cows by clearing heat, tonifying qi, and improving blood and milk circulation. The study aimed to determine the anti-inflammatory and antimicrobial efficacy of Qicao Rukang powder in treating subclinical mastitis in dairy cows at the manufacturer's recommended dose. Methods. Forty (40) Holstein dairy cows with milk somatic cell count (SCC) ≥ 500,000 cellml−1 were randomly assigned to treatment (n = 20) and control (n = 20) groups. Cows in the treatment group were administered with 150 grams of Qicao Rukang powder orally for five days, while the control group received no treatment. The authors analyzed the milk SCC, milk composition, bacteriological cure rate of the drug, blood serum levels of interleukins (IL-6, IL-1β, and IL-8), tumor necrosis factor (TNF-α), and interferon gamma (INF-γ) quantified by using ELISA kits on day 0 and day 6. Results. SCC of the treated group reduced very significantly (P < 0.001) compared with the control group. Milk fat, protein, and total solids increased significantly (P < 0.05) after treatment, whereas lactose and milk urea nitrogen levels showed a nonsubstantial rise. The bacteriological cure percentage of Qicao Rukang powder therapy was 77.8% for Aeromonas spp. (14 of 18), 75% for Pseudomonas spp. (6 of 8), and 100% for Acinetobacter spp. and Enterococcus spp. giving 81.8% cured for all isolates (27 of 33). Only 26.7% (8 of 30) of untreated cows recovered spontaneously. Analysis of IL-1β, IL-6, and INF-γ in the blood serum of the treated group revealed a significant decrease (P < 0.01) with nonsignificant rises in TNF-α and IL-8 levels. Conclusions. This research demonstrates that Qicao Rukang powder has potent antibacterial and anti-inflammatory actions, supporting its use as an alternative to conventional treatment for subclinical dairy cow mastitis. However, further investigations will be required to explain the role of the active ingredients and the mechanisms involved in the pharmacological activities of the Qicao Rukang powder. [ABSTRACT FROM AUTHOR]

Here, we evaluated the in vivo skin-protective effects of topical applications of Panax ginseng C. A. Meyer extract (PG2) and its phenolic acid- (PA-) based components against UVB-induced skin photoaging. PG2 or PA applied to skin of hairless mice after UVB-irradiation alleviated UVB-induced effects observed in untreated skin, such as increased transepidermal water loss (TEWL), increased epidermal thickness, and decreased stratum corneum water content without affecting body weight. Moreover, PG2 and PA treatments countered reduced mRNA-level expression of genes encoding filaggrin (FLG), transglutaminase-1 (TGM1), and hyaluronan synthases (HAS1, HAS2, and HAS3) caused by UVB exposure and reduced UVB-induced collagen fiber degradation by inhibiting the expression of matrix metalloproteinase genes encoding MMP-1, MMP-2, and MMP-9. Meanwhile, topical treatments reduced cyclooxygenase-2 (COX-2) mRNA-level expression in photodamaged skin, leading to the inhibition of interleukin-1β (IL-1β) and interleukin-6 (IL-6) mRNA-level expression. Thus, ginseng phenolic acid-based preparations have potential value as topical treatments to protect skin against UVB-induced photoaging. [ABSTRACT FROM AUTHOR]

Introduction. The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. Methods. A search of the literature was performed using PubMed by pairing "interstitial cells of Cajal" with "medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM)." Results. From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, 半夏泻心汤, and Yukgunja-tang, 六君子汤) have been shown to modulate ICC functions by both clinical and preclinical data. Conclusion. This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents. [ABSTRACT FROM AUTHOR]

Alternation in culture environment due to cell-cell communications can rejuvenate the biological activity of aged/differentiated cells and stimulate the expression of pluripotency markers. Dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) are promising candidates in dental tissue regeneration. However, the molecular network that underlies cell-cell communications between dental-derived cells and the microenvironment remains to be identified. To elucidate the signaling network that regulates the pluripotency of DPCs and PDLCs, proliferation, apoptosis, cell cycle, and the expression of Oct-4/Sox2/c-Myc in DPCs and PDLCs with indirect/direct coculture were examined. PCR arrays were constructed to identify genes that were differentially expressed, and the results were confirmed by a rat model with injury. Further research on the mechanism of the related signaling pathways was investigated by overexpression/silence of STAT3, ChIP, the dual-luciferase reporter assay, and EMSA. We found that the proliferation and apoptosis of DPCs and PDLCs were inhibited, and their cell cycles were arrested at the G0/G1 phase after coculture. Oct-4, Sox2, and STAT3 expression significantly increased and PAX5 expression decreased in the coculture systems. Oct-4/Sox2/STAT3/PAX5 was actively expressed in the rat defect model. Moreover, STAT3 was directly bound to the Oct-4 and Sox2 gene promoter regions and activated the expression of those genes. Our data showed that the pluripotency of DPCs and PDLCs was enhanced through cell-cell communication. STAT3 plays essential roles in regulating the pluripotency of DPCs and PDLCs by targeting Oct-4 and Sox2 both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background. Newts have impressive regenerative capabilities, but it remains unclear about the role of epigenetic regulation in regeneration process. We herein investigated histone modifications in newt tail tissue cells following amputation. Methods and Results. Iberian ribbed male newts (6-8 months old) were suffered to about 1.5 cm length of amputation of their tails for initiating regeneration process, and the residual stump of tail tissues was collected for immunohistochemical analysis 3 days later. Compared to the tissue cells of intact tails, c-kit-positive stem cells and PCNA-positive proliferating cells were significantly higher in tails suffered to amputation (P < 0.001). Amputation also significantly induced the acetylation of H3K9, H3K14, and H3K27 in cells of the tails with amputation (P < 0.001), but did not significantly change the methylation of H3K27 (P = 0.063). Conclusion. These results suggest that epigenetic regulation likely involves in newt tail regeneration following amputation. [ABSTRACT FROM AUTHOR]

Mycotoxin contamination in feedstuffs is a worldwide problem that causes serious health issues both in humans and animals, and it contributes to serious economic losses. Deoxynivalenol (DON) and T-2 toxin (T-2) are major trichothecene mycotoxins and are known to challenge mainly intestinal barrier functions. Polyphenolic rosmarinic acid (RA) appeared to have antioxidant and anti-inflammatory properties in vitro. The aim of this study was to investigate protective effects of RA against DON and T-2 or combined mycotoxin-induced intestinal damage in nontumorigenic porcine cell line, IPEC-J2. It was ascertained that simultaneous treatment of DON and T-2 (DT2: 1 μ mol / L DON + 5 nmol / L T − 2) for 48 h and 72 h reduced transepithelial electrical resistance of cell monolayer, which was restored by 50 μmol/L RA application. It was also found that DT2 for 48 h and 72 h could induce oxidative stress and elevate interleukin-6 (IL-6) and interleukin-8 (IL-8) levels significantly, which were alleviated by the administration of RA. DT2 administration contributed to the redistribution of claudin-1; however, occludin membranous localization was not altered by combined mycotoxin treatment. In conclusion, beneficial effect of RA was exerted on DT2-deteriorated cell monolayer integrity and on the perturbated redox status of IPEC-J2 cells. [ABSTRACT FROM AUTHOR]

Objectives. To observe the effect of Inonotus obliquus polysaccharide (IOP) on the proliferation, invasion, migration, and apoptosis of osteosarcoma cells and to elucidate its underlying molecular mechanism. Methods. IOP was extracted from Inonotus obliquus, human osteosarcoma MG-63 cells and U2OS cells were cultured in vitro, and the effects of IOP on the proliferation, migration, invasion, and apoptosis of MG-63 cells and U2OS cells were determined by CCK-8 assays, cell scratch assays, transwell assays, and flow cytometry, respectively. Western blot was used to detect the expression of related proteins in the Akt/mTOR and NF-κB signaling pathways. Results. Compared with the control group, MG-63 cells and U2OS cells treated with IOP of 80 μg/ml, 160 μg/ml, and 320 μ g/ml in the experimental group had significantly lower proliferation activity, decreased migration and invasion ability, and increased apoptosis rate (P < 0.05). Furthermore, IOP could significantly inhibit the activation of the Akt/mTOR and NF-κB signaling pathway (P < 0.05). Conclusion. IOP can regulate the proliferation, migration, invasion, and apoptosis of osteosarcoma cells by inhibiting the activation of the Akt/mTOR signaling pathway. It has antitumor activity on osteosarcoma and has the potential of clinical application in osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade fibroblastic mesenchymal tumor derived from the dermis. The aim of this retrospective analysis was to summarize the clinicopathological data from our cases and published cases to offer more evidence for the recognition of dermatofibrosarcoma protuberans (DFSP). A total of 6 breast DFSP patients who had received treatment in our hospital were retrospectively enrolled, and detailed clinicopathological data were gathered for analysis. The median age was 29.5 years (ranging from 17 to 42 years). Most cases presented a red or brown-red, mobile, well-circumscribed, protruding, breast mass (ranging from 1 to 3 cm). For histopathology, all cases (6/6) showed a storiform pattern of spindle cells that were positive for CD34 (6/6) and Vimentin (5/6) and negative for smooth muscle actin (0/6) and S-100 protein (0/6). The majority of patients (5/6) underwent wide local excision, with 2 cases treated with radiotherapy. With a median follow-up of 36 months, all 6 patients survived without recurrence or metastasis. The PubMed database was used to search for similar cases. Eventually, 36 cases were included in this review, while cases without detailed clinical information or not reported in English were excluded from the analysis. To summarize, DFSP of the breast is an extremely rare malignancy characterized by spindle tumor cells arranged in a storiform pattern and positivity for CD34. The core needle biopsy is one of the crucial methods for its preoperative diagnosis. Management of DFSP is mainly based on surgical excision. It is prone to local recurrence, so long-term follow-up is required. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of berberine (Berb) on dexamethasone- (Dex-) induced injury of human tendon cells and its potential mechanism. Methods. CCK-8 assay was used to explore the appropriate concentration of Dex-induced injury of tendon cells and the doses of Berb attenuates Dex cytotoxicity; cell wound healing assay was used to detect the effects P < 0.05 of Berb and Dex on the migration ability of tendon cells; flow cytometry was used to measure cell apoptosis; DCF DA fluorescent probe was used to measure the ROS activity of cells. Western blotting was used to detect the expression of phenotype related factors including smooth muscle actin α (SMA-α), type I collagen (Col I), col III, apoptosis-related factors, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and PI3K/AKT. Results. CCK-8 assay showed that 1–100 μM Dex significantly inhibited the proliferation of tendon cells in a concentration-dependent manner P < 0.05 , where the inhibitory effect of 100 μM Dex was most significant P < 0.005 , and the pretreatment of 150, 200 μM Berb could reverse those inhibitions (all P < 0.05). Compared with the control group, Dex significantly inhibited cell migration P < 0.05 , while Berb pretreatment could enhance cell migration P < 0.05 . Flow cytometry and ROS assay showed that Dex could induce apoptosis and oxidative stress response of tendon cells (all P < 0.05), while Berb could reverse those responses P < 0.05 . Western blot showed that Dex could inhibit the expression of the col I and III as well as α-SMA (all P < 0.05) and enhance the expression of apoptosis-related factors including cleaved caspase-3 and cleaved caspase-9 (all P < 0.05). Besides, Dex could also inhibit the activation of the PI3K/AKT signaling pathway (all P < 0.05), thus affecting cell function, while Berb treatment significantly reversed the expression of those above proteins (all P < 0.05). Conclusion. Berb attenuated DEX induced reduction of proliferation and migration, oxidative stress, and apoptosis of tendon cells by activating the PI3K/AKT signaling pathway and regulated the expression of phenotype related biomarkers in tendon cells. However, further studies are still needed to clarify the protective effects of Berb in vivo. [ABSTRACT FROM AUTHOR]

Background. Gestational diabetes mellitus (GDM) seriously affects the health of mothers and infants. The high-glucose-induced inhibition in trophoblast cell viability is an important event in GDM pathogenesis. This study evaluated the expression and clinical significance of miR-136 in GDM patients, and the biological function and related mechanisms of miR-136 in the regulation of trophoblast cell proliferation were explored. Methods. The expression of miR-136 in serum and placenta of GDM patients was measured using quantitative Real-Time PCR. Trophoblast cells were stimulated with high-glucose medium to mimic the pathological changes of GDM, and the effect of miR-136 was examined by CCK-8 assay. A luciferase reporter assay was used to confirm the target gene of miR-136, and the relationship of E2F transcription factor 1 (E2F1) with miR-136 in GDM was further analyzed. Results. miR-136 expression was significantly elevated in GDM serum and tissue samples. By high-glucose treatment, trophoblast cell proliferation was inhibited and miR-136 expression was promoted. The knockdown of miR-136 could promote the proliferation of trophoblast cells exposed to high glucose, whereas the overexpression of miR-136 could suppress it. In addition, E2F1 was identified as a target gene of miR-136, which could mediate the regulatory effect of miR-136 on trophoblast cell proliferation. Conclusion. Collectively, miR-136 expression is increased in both serum and placental tissues in GDM patients, and miR-136 mediates the inhibiting effect of high glucose on trophoblast cell viability by targeting E2F1. [ABSTRACT FROM AUTHOR]

Protecting foods from contamination applying peptides produced by lactic acid bacteria is a promising strategy to increase the food quality and safety. Interacting with the pathogen membranes might produce visible changes in shape or cell wall damage. Previously, we showed that the peptides produced by Lactobacillus plantarum UTNGt2, Lactobacillus plantarum UTNCys5-4, and Lactococcus lactis subsp. lactis UTNGt28 exhibit a broad spectrum of antibacterial activity against several foodborne pathogens in vitro. In this study, their possible mode of action against the commensal microorganism Salmonella enterica subsp. enterica ATCC51741 was investigated. The target membrane permeability was determined by detection of beta-galactosidase release from ONPG (o-nitro-phenyl-L-D-galactoside) substrate and changes in the whole protein profile indicating that the peptide extracts destroy the membrane integrity and may induce breaks in membrane proteins to some extent. The release of aromatic molecules such as DNA/RNA was detected after the interaction of Salmonella with the peptide extract. Transmission electronic microscopy (TEM) micrographs depicted at least four simultaneous secondary events after the peptide extract treatment underlying their antimicrobial actions, including morphological alterations of the membrane. Spheroplast and filament formation, vacuolation, and DNA relaxation were identified as the principal events from the Gt2 and Cys5-4 peptide extracts, while Gt28 induced the formation of ghost cells by release of cytoplasmic content, filaments, and separation of cell envelope layers. Gel retarding assays indicate that the Gt2 and Gt28 peptide extracts are clearly binding the Salmonella DNA, while Cys5-4 partially interacted with Salmonella genomic DNA. These results increased our knowledge about the inhibitory mechanism employed by several peptide extracts from native lactic acid bacteria against Salmonella. Further, we shall develop peptide-based formulation and evaluate their biocontrol effect in the food chains. [ABSTRACT FROM AUTHOR]

Isolation of active components of therapeutic plants and discovering molecular mechanisms play a pivotal role in therapy of diabetes. This study aimed to determine the antidiabetic mechanism of an oligosaccharide isolated from Rosa canina (RCO) by measuring the expression of some miRNAs and their targets involved in autophagy. RCO was extracted and characterized by using HPLC and spectroscopic methods. Rin‐5F cells were treated with STZ and RCO alone and in combination. The viability of the cells and the expression of miR‐21, miR‐22, Akt, ATG5, Beclin1, LC3A, and LC3B were analyzed using MTT assay, and qRT‐PCR, respectively. Oligosaccharide fraction could improve the viability of RCO‐treated cells as compared to STZ‐treated cells. Further, the expression of autophagy markers was increased in RCO‐treated diabetic cells compared to STZ‐treated cells. The results indicated that the antidiabetic effects of the oligosaccharide components of R. canina seem to be mediated by modulation of autophagy pathway. Practical applications: Given effectiveness of an oligosaccharide fraction isolated from Rosa canina in management of diabetes in STZ‐induced diabetic rats, we have intention to scrutinize its molecular mechanism as modulation of autophagy pathway in STZ‐treated Rin‐5F cells. It is expected that the results paved the way to speculate novel antidiabetic strategies. [ABSTRACT FROM AUTHOR]

Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here, we show the CHD7 expression increases with osteogenic differentiation. The knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and the decreased expression of osteogenesis-related genes. Conversely, the CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the downregulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, the overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R. [ABSTRACT FROM AUTHOR]

Exosomes can reach distant tissues through blood circulation to communicate directly with target cells and rapidly regulate intracellular signals. Exosomes play an important role in cardiovascular pathophysiology. Different exosomes derived from different sources, and their cargos have different mechanisms of action. In addition to being biomarkers, exosomes also have a certain significance in the diagnosis, treatment, and even prevention of cardiovascular diseases. Here, we provide a review of the up-to-date applications of exosomes, derived from various sources, in the prognosis and diagnosis of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Summary: Lithium‐ion pouch cells are widely used in electric vehicles because of their high energy density than other structures. There is an unavoidable external surface pressure between the cells in the process of packing and driving of electric vehicles. The influence of external surface pressure on the main properties of the lithium‐ion pouch cell has been studied, which is of great significance to packing batteries and reusing retired cells. In this study, a testing device applied for the measurement of constant external surface pressures of lithium‐ion pouch cells was first proposed and the different pressure stress‐strain distribution on the external surface of cells under semirigid material pads were analyzed by simulation. The effects of pressure on the capacity, internal resistance, and open circuit voltage of fresh and aged LiNixCoyMnzO2 (NCM) lithium‐ion pouch cells are analyzed through experiments under 1 Mpa external surface pressure. The results show that the internal resistance of fresh cells tends to decrease. The average percentage of the maximum reduction of internal resistance is 13.28%. The experiments also demonstrate that the capacity of aging cells increased by 2.3%. Irreversibility of capacity improvement indicates applying appropriate external surface pressure can improve the secondary utilization efficiency of aging cells. [ABSTRACT FROM AUTHOR]

Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNFα and IL1β were significantly suppressed following a second LPS challenge (p < 0.001) on day 7 after first LPS stimulation. However, the analysis of cellular metabolism did not reveal any noteworthy alterations between tolerant and nontolerant THP-1 monocytes. No quantitative differences in ATP and NADH synthesis or participating enzymes of energy metabolism occurred. Our data demonstrate that the function and epigenetic modifications of septic and tolerized monocytes can be examined in vitro with the help of our LPS model. Changes in CpG site methylation and monocyte function point to a correlation between epigenetic modification in metabolic pathways and reduced monocyte function under postseptic conditions. [ABSTRACT FROM AUTHOR]

Titanium (Ti) is widely used in oral implants. However, there is still a challenge to promote the osseointegration of bone tissue on the surface of Ti. To solve this problem, we prepared novel gradient nanostructured (GNS) Ti and studied the effect of GNS on the adhesion, proliferation, and apoptosis of MG63 cells in vitro. The results demonstrated that the GNS Ti promoted the adhesion effect and proliferation of MG63 cells better than the annealed Ti, while the ability of GNS Ti to inhibit cell apoptosis was better than that of the annealed Ti, the preliminary mechanism of which indicated by this study might be the enhanced mineralization capacity, protein adsorption ability, and hydrophilicity of the GNS Ti due to its specific nanostructure which improved the cell behaviours. The results in this study provide the theoretical and experimental foundations for the applications of GNS Ti in dental implants and joint replacements. [ABSTRACT FROM AUTHOR]

Objective. To investigate the intervention effect and mechanism of Aconite and Angelica sinensis on myocardial ischemia rats with Yang deficiency and blood stasis. Methods. SPF-class SD rats were randomly divided into low-dose and high-dose groups. Each group was divided into control group, model group, and drug-administered group (FZ, DG, FG; 1 : 0.5, 1 : 1, 1 : 2). A rat model was prepared by intraperitoneal injection of hydrocortisone and isoproterenol plus cold stimulation. Each group was given corresponding decoction or distilled water for 14 days. The behavioral changes of rats in each group were observed. The morphological changes of rats cardiomyocytes were observed by HE staining. The average optical density (MOD value) and percentage of positive cells of Bcl-2, Bax, and Akt were determined by immunohistochemical staining method, and PEIs were calculated. Western blot and RT-PCR were used to determine the expression of PI3K, Caspase-3, Akt protein, and gene expression. Results. The compatibility of Aconite and Angelica sinensis improved the morphology of rat cardiomyocytes, increased the PEI values of Akt and Bcl-2 protein, and decreased the PEI values of Bax protein (P < 0.01). The compatibility reduced the expression of Caspase-3 protein of rat myocardium and increased the protein expression of p-Akt, PI3K, and p-PI3K (P < 0.01). The compatibility also significantly reduced the expression of Caspase-3 mRNA and increased the expression of PI3K mRNA and Akt mRNA (P < 0.05 or P < 0.01), and the effect of high-dose FG (1 : 2) group is the best. Conclusions. The method of preparing a rat model of myocardial ischemia with Yang deficiency and blood stasis was feasible. The compatibility of Aconite and Angelica sinensis reduced myocardial fibrosis and inflammatory reaction, protected ischemic cardiomyocytes, and reduced myocardial injury, whose mechanism may be related to the regulation of PI3K/Akt pathway. The compatible group had better intervention effects than Aconite or Angelica sinensis alone. The best one was high-dose FG (1 : 2). [ABSTRACT FROM AUTHOR]

Hidradenocarcinoma (HC) is a rare malignant sweat gland tumor with metastatic potential primarily located in the head, neck, and trunk. We present an unusual case of a large lower extremity Clear Cell HC managed with surgical resection and adjuvant locoregional radiation after excluding lymph node involvement. [ABSTRACT FROM AUTHOR]

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells obtained from human menstrual blood, whose positive therapeutic effects have been validated in several experimental models. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, plays an important role in the migration of mesenchymal stromal cells. The purpose of this study was to investigate the role of the SDF-1/CXCR4 pathway in the therapeutic effects of ERCs in a mouse sepsis model. Through preexperiment and confirmation, wild-type C57BL/6 mice were intraperitoneally injected with 10 mg/kg lipopolysaccharide (LPS). The therapeutic effects of ERCs with different pretreatments were evaluated by assessing sepsis-related symptoms, detecting tissue damage and measuring levels of inflammatory and oxidative stress-related factors. The in vitro experiments demonstrated that there was a much higher CXCR4 expression on ERCs when they were cocultured with SDF-1. The ex vivo experiment results showed that SDF-1 expression significantly increased in mouse tissues. Further experiments also confirmed that, compared with the unmodified ERC treatment group, SDF-1 pretreatment significantly enhanced the therapeutic effects of ERCs on alleviating sepsis symptoms, ameliorating pathological changes, reducing Bax level, and increasing Bcl-2 and PCNA expressions in mouse liver tissues. Furthermore, it was also found that SDF-1-pretreated ERCs contributed to reducing the levels of proinflammatory cytokines (TNF-α, IL-1β) and increasing the levels of anti-inflammatory factors (IL-4, IL10) in mouse serum, liver, and lung. Moreover, SDF-1-pretreated ERCs could also significantly decrease the levels of iNOS and MDA and increase the expression of Nrf2, HO-1, and SOD in liver tissues. Taken together, these results indicate that SDF-1 pretreatment plays a key role in improving the therapeutic effects of ERCs in alleviating sepsis-related symptoms, reducing tissue damage, regulating inflammatory imbalance, and relieving oxidative stress in a mouse sepsis model, which provides more possibilities for the clinical application of ERCs in sepsis and relevant diseases. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effect of Mn3O4 nanoparticles (Mn3O4NPs) on inflammatory factors induced by lipopolysaccharide (LPS) in human tendon cells and its mechanism. Methods. The Mn3O4NPs were synthesized by a hydrothermal method. RT-qPCR was used to detect the expression levels of miRNAs related to inflammation in human tendon cells. The expression level of NLRP1 (NOD-like receptor containing pyrin domain 1) was measured by Western blotting. ELISA assay was used to measure the level of TNF-α, IL-1β, IL-4, and IL-10. The relationship between miR-181a-5p and NLRP1 was verified by dual-luciferase reporter assay. Results. Mn3O4NPs produced in this study were brown spherical particles with an average size of 7-10 nm. Mn3O4NP treatment significantly reduced the levels of TNF-α and IL-1β but increased the levels of IL-4 and IL-10 in the human tendon cells induced by LPS. In addition, Mn3O4NP treatment remarkably increased the expression level of miR-181a-5p. NLRP1 is one of the targets of miR-181a-5p, and miR-181a-5p downregulated its expression. Further study showed that Mn3O4NPs could alleviate the inflammatory response of human tendon cells induced by LPS by upregulating miR-181a-5p and thus downregulating the expression of NLRP1. Conclusion. Mn3O4NPs affect the expression of inflammatory cytokines in the human tendon cells induced by LPS by modulating the molecular axis of miR-181a-5p/NLRP1. [ABSTRACT FROM AUTHOR]

Leucoproliferative Theileria parasites possess the unique capability to transform their bovine host cell, resulting in tumour‐like characteristics like uncontrolled proliferation. The molecular mechanisms underlying this parasite‐dependent process are only poorly understood. In the current study, bioinformatic analysis of the Theileria annulata surface protein (TaSP) from different T. annulata isolates identified a conserved CDK1 phosphorylation motif T131PTK within the extracellular, polymorphic domain of TaSP. Phosphorylation assays with radioactively labelled ATP as well as ELISA‐based experiments using a phospho‐threonine‐proline (pThr‐Pro) antibody revealed, that CDK1‐cyclin B specifically phosphorylates T131, identifying TaSP as a substrate in vitro. Confocal microscopy and proximity ligation assays suggest an interaction between CDK1 and TaSP in T. annulata‐infected cells. Further studies demonstrated a nearly complete co‐localization of the pThr‐Pro signal and TaSP only in cells in interphase, pointing towards a cell cycle‐dependent event. Immunostainings of isolated, non‐permeabilized schizonts confirmed the presence of the pThr‐Pro epitope on the schizont's surface. Lambda phosphatase treatment abolished the pThr‐Pro signal of the schizont, which was reconstituted by the addition of CDK1‐cyclin B. Treatment of T. annulata‐infected cells with the CDK1 inhibitor purvalanol A resulted in morphological changes characterized by tubulin‐rich cell protrusions and an extension of the schizont, and a dose‐dependent reduction of BrdU incorporation and Ki67 staining of T. annulata‐infected cells, demonstrating a clear impact on the Theileria‐dependent proliferation of the bovine host cell. Our data reveal the parasite surface protein TaSP as a target for the host cell kinase CDK1, a major player during cell division. Targeting the uncontrolled proliferation of Theileria‐infected cells is a novel and reasonable approach to limit parasite load in order to facilitate a successful cellular immune response against the parasite. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the role of SPARC in the antiproliferation effect of MMC on human Tenon's fibroblasts (HTF). Method. Sixteen PACG patients aged 59 ± 10 years (31–72 years), including 6 males and 10 females, were recruited. Tenon tissue was harvested during filtering surgery. Cell density was evaluated after MMC application with different concentrations and application times, by which the optimized MMC application modality was determined. MMC, si-SPARC, or SPARC protein was used when needed to evaluate the cell densities under different conditions, by which the role of SPARC in MMC-mediated antifibrotic process was identified. Results. Considering that the cell densities, as well as SPARC expression on mRNA and protein levels, are relatively stable when the MMC concentration is higher than 0.02% and exposure time longer than 90 s, we chose the MMC application pattern with 0.02% and 90 s as an optimized pattern for the downstream work. Compared to control, the si-SPARC and MMC downregulated the SPARC protein by 91% (P < 0.01) and 65% (P < 0.01) and mRNA by 96% (P < 0.01) and 64% (P < 0.01), respectively. MMC decreases the cell densities by 53.50% compared to control. si-SPARC + MMC dramatically deceased the cell density no matter compared to the control group (P < 0.01) or MMC group (P < 0.01); correspondingly, the relative collagen gel area in the MMC + si-SPARC group was higher than that in the MMC group or si-SPARC group (P < 0.05). The reactive oxygen species expression in the MMC + si-SPARC group is higher than that in the MMC group (P < 0.05). Conclusion. This study demonstrates that in HTF, (1) MMC downregulates the expression of SPARC in protein and mRNA levels; (2) SPARC depletion has synergistic effect on the antifibrotic effect of MMC; and (3) reactive oxygen species are the possible mediator in the antifibrotic effect of MMC and si-SPARC. [ABSTRACT FROM AUTHOR]

Massive multiple-input multiple-output techniques have attracted wide attention as one of the key technologies of 5G. Pilot reuse based on the same pilot sequence is necessary among different users due to limited pilot resources. In this study, a pilot reuse mode based on continuous pilot reuse factors is proposed to pursue a flexible pilot reuse mode with high spectral efficiency (SE). In this mode, users in every cell are grouped, and different groups use different pilot reuse factors. Therefore, any overall pilot reuse factor is achieved to increase the flexibility of pilot reuse considerably. A theoretical analysis proves that the proposed pilot reuse based on continuous pilot reuse factors is superior to the traditional pilot reuse based on single pilot reuse factor to some extent in terms of SE. A new method to search the optimal pilot reuse based on continuous pilot reuse factors is also introduced. Simulation results demonstrate that, in most cases, the optimal pilot reuse mode based on continuous pilot reuse factors is better than the traditional mode. Such superiority still exists under a limited number of antennas. [ABSTRACT FROM AUTHOR]

Objective. We investigated the efficacy of astragalus polysaccharide (APS) combined with budesonide and the effect on expressions of peripheral NK cells and Treg cells and the molecular mechanism in mice with bronchial asthma. Methods. In this study, we established a mouse model of asthma. Four groups of BaLB/C mice were developed; control group had no asthma induction, and the other three groups of mice were sensitized by OVA (Ovalbumin), OVA + budesonide, and OVA + APS + budesonide. Flow cytometry was used to determine the proportion of NK cells and Treg cells. Levels of cytokines IL-4 and IL-10 were detected using RT-PCR and ELISA. Results. Asthma mice treated with APS + budesonide showed alleviated airway resistance compared to model mice (P < 0.05). The percentage of dendritic cells (DCs) was reduced (P < 0.05), while anti-inflammatory NK cells and Treg cells significantly increased after APS + budesonide treatment (P < 0.05). Further, APS + budesonide treatment resulted in improvements in IL-4 and IL-10 mRNA and protein levels (P < 0.05). Conclusion. APS combined with budesonide medication may regulate expressions of DCs cells and related cytokines, reliving clinical symptom of bronchial asthma. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process regulated by multiple signals and consisting of several phases known as haemostasis, inflammation, proliferation, and remodelling. Keratinocytes, endothelial cells, macrophages, and fibroblasts are the major cell populations involved in wound healing process. Hypoxia plays a critical role in this process since cells sense and respond to hypoxic conditions by changing gene expression. This study assessed the in vitro expression of 77 genes involved in angiogenesis, metabolism, cell growth, proliferation and apoptosis in human keratinocytes (HaCaT), microvascular endothelial cells (HMEC-1), differentiated macrophages (THP-1), and dermal fibroblasts (HDF). Results indicated that the gene expression profiles induced by hypoxia were cell-type specific. In HMEC-1 and differentiated THP-1, most of the genes modulated by hypoxia encode proteins involved in angiogenesis or belonging to cytokines and growth factors. In HaCaT and HDF, hypoxia mainly affected the expression of genes encoding proteins involved in cell metabolism. This work can help to enlarge the current knowledge about the mechanisms through which a hypoxic environment influences wound healing processes at the molecular level. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury is unavoidable during organ transplantation and impacts graft quality. New paradigms are emerging including preservation at higher temperature than "hypothermia" or "cold": although 4°C remains largely used for kidney preservation, recent studies challenged this choice. We and others hypothesized that a higher preservation temperature, closer to physiological regimen, could improve organ quality. For this purpose, we used an in vitro model of endothelial cells exposed to hypoxia-reoxygenation sequence (mimicking IR) and an ex vivo ischemic pig kidneys static storage model. In vitro, 19°C, 27°C, and 32°C provided protection against injuries versus 4°C, by reducing cell death, mitochondrial dysfunction, leukocyte adhesion, and inflammation. However, ex vivo, the benefits of 19°C or 32°C were limited, showing similar levels of tissue preservation damage. Ex vivo 4°C-preserved kidneys displayed a trend towards reduced damage, including apoptosis. Macrophage infiltration, tubulitis, and necrosis were increased in the 19°C and 32°C versus 4°C preserved kidneys. Thus, despite a trend for an advantage of subnormothermia as preservation temperature, our in vitro and ex vivo models bring different insights in terms of preservation temperature effect. This study suggests that temperature optimization for kidney preservation will require thorough investigation, combining the use of complementary relevant models and the design of elaborated preservation solution and new technologies. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFβ, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM. [ABSTRACT FROM AUTHOR]

Despite a large number of studies reporting a variety of biological and pharmacological activities of Momordica charantia, its skin protective properties are poorly understood. The present study aimed to explore the skin protective properties of Momordica charantia methanol extract (Mc-ME) and the underlying mechanism in keratinocytes, fibroblasts, and melanocytes. Mc-ME exhibited an antioxidative property by decreasing radical levels in HaCaT keratinocytes and a cytoprotective property in H2O2-damaged HaCaT cells, which was mediated by increasing the expression or activation of Kelch-like ECH-associated protein 1 (KEAP1), HO-1, p85/PI3K, and AKT. Mc-ME was also active against wrinkle formation by regulating the activity or expression of tissue remodeling factors such as elastase, type 1 collagen, and matrix metalloproteinase (MMP)-1 and -9 and tissue-protecting enzymes such as hemeoxygenase-1 (HO-1) and sirtuin 1 (SIRT1) in NIH3T3 fibroblasts and HaCaT cells, in addition to increasing the proliferation of HaCaT cells. Mc-ME also showed antidehydration properties by inducing the expression of natural moisturizing factors such as filaggrin (FLG), transglutaminase-1 (TGM-1), and hyaluronic acid synthase (HAS)-1, -2, and -3 in HaCaT cells. Moreover, Mc-ME showed an antimelanogenic property by inhibiting the synthesis and secretion of melanin from B16F10 melanoma cells via suppression of tyrosinase activity. Taken together, these results suggest that Mc-ME plays a skin protective role through its antioxidative, cytoprotective, skin remodeling, moisturizing, and antimelanogenic properties and might be a new and promising skin protective cosmeceutical. [ABSTRACT FROM AUTHOR]

Although mechanical properties of a single cell as well as its mechanical response to stimulation are significant for mechanotransduction, it is difficult to quantitatively identify the viscoelasticity of a cell. This study proposes a methodology to determine the viscoelastic parameters for a single cell combining flow chamber experiment and fluid-structure coupled finite element model. The observation from the experiment is used to compare with the deformation response of the cell with different parameters in the finite element model with standard linear solid constitute model, which are adjusted until the two displacement response curves from the experiment and the simulation accord with each other, and then the corresponding combination of the viscoelastic parameters is determined to represent the viscoelasticity of the cell. The proposed methodology is applied on osteocytes in this study but can be generalized to other cells. The results indicate that both k1 and k2 of an osteocyte are in the order of several hundred Pa and η is in the order of kPa·s. [ABSTRACT FROM AUTHOR]

Extracellular ATP and trophic factors released by exocytosis modulate in vivo proliferation, migration, and differentiation in multipotent stem cells (MpSC); however, the purinoceptors mediating this signaling remain uncharacterized in stem cells derived from the human olfactory epithelium (hOE). Our aim was to determine the purinergic pathway in isolated human olfactory neuronal precursor cells (hONPC) that exhibit MpSC features. Cloning by limiting dilution from a hOE heterogeneous primary culture was performed to obtain a culture predominantly constituted by hONPC. Effectiveness of cloning to isolate MpSC-like precursors was corroborated through immunodetection of specific protein markers and by functional criteria such as self-renewal, proliferation capability, and excitability of differentiated progeny. P2 receptor expression in hONPC was determined by Western blot, and the role of these purinoceptors in the ATP-induced exocytosis and changes in cytosolic Ca2+ ([Ca2+]i) were evaluated using the fluorescent indicators FM1-43 and Fura-2 AM, respectively. The clonal culture was enriched with SOX2 and OCT3/4 transcription factors; additionally, the proportion of nestin-immunopositive cells, the proliferation capability, and functionality of differentiated progeny remained unaltered through the long-term clonal culture. hONPC expressed P2X receptor subtypes 1, 3-5, and 7, as well as P2Y2, 4, 6, and 11; ATP induced both exocytosis and a transient [Ca2+]i increase predominantly by activation of metabotropic P2Y receptors. Results demonstrated for the first time that ex vivo-expressed functional P2 receptors in MpSC-like hONPC regulate exocytosis and Ca2+ signaling. This purinergic-triggered release of biochemical messengers to the extracellular milieu might be involved in the paracrine signaling among hOE cells. [ABSTRACT FROM AUTHOR]

Microglia, the central nervous system's innate immune cells, mediate neuroinflammation and are implicated in a variety of neuropathologies. The present study investigated the antineuroinflammatory and neuroprotective effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in lipopolysaccharide- (LPS-) stimulated murine BV2 microglia. BV2 cells were pretreated with GBH, fluoxetine (FXT), or amitriptyline (AMT) for 1 h and then stimulated with LPS (100 ng/mL). The expression levels of nitric oxide (NO), cytokines, and chemokines were determined by the Griess method, ELISA, or real-time PCR. Western blotting was used to measure various transcription factors and mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt activity. GBH significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, macrophage inhibitory protein- (MIP-) 1α, macrophage chemoattractant protein- (MCP-) 1, and IFN-γ inducible protein- (IP-) 10, regulated upon activation normal T cell expressed sequence (RANTES) in a dose-dependent manner. Expression of nuclear factor- (NF-) κB p65 was significantly decreased and phosphorylation of extracellular signal-regulated kinase (Erk), c-Jun NH2-terminal kinase (JNK), and PI3K/Akt by GBH, but not p38 MAPK, was decreased. Furthermore, production of anti-inflammatory cytokine IL-10 was increased and Heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/cAMP response element-binding protein (CREB) pathway, collectively indicating the neuroprotective effects of GBH. We concluded that GBH may suppress neuroinflammatory responses by inhibiting NF-κB activation and upregulating the neuroprotective factor, HO-1. These results suggest that GBH has potential as anti-inflammatory and neuroprotective agents against microglia-mediated neuroinflammatory disorders. [ABSTRACT FROM AUTHOR]