Search

• IL-35 release in clinical ARDS but reduced in non-survivor, suggesting anti-inflammatory potential of IL-35 in clinical ARDS. • Recombinant IL-35 treatment could improve survival in experimental ARDS. • Its protective effect is promoting differentiation of Helios+Foxp3+Tregs to improve uncontrolled inflammation in ARDS. • IL-35 could be a novel cytokine-targeted for the regulation of T cell differentiation in ARDS development. Regulatory T lymphocytes are important targets for the treatment of acute respiratory distress syndrome (ARDS). IL-35 is a newly identified IL-12 cytokine family member that plays an important protective role in a variety of immune system diseases by regulating Treg cell differentiation; however, the role of IL-35 in the pathogenesis of ARDS is still unclear. Here, we found that IL-35 was significantly elevated in adult patients with ARDS compared to controls. Additionally, IL-35 was positively and significantly correlated with IL-6, IL-10 and the oxygenation index (PaO2/FiO2 ratio) but negatively correlated with TNF-α, IL-1β and APACHE II score during ARDS. Moreover, the proportion of Treg/CD4+ cells in the peripheral blood of ARDS patients and the expression of NF-κB in PMBCs were significantly higher than in healthy individuals. Recombinant IL-35 improved survival in a murine model of CLP-induced ARDS. Additionally, IL-35 administration decreased the inflammatory response, as reflected by lower levels of cytokines (including IL-2, TNF-α, IL-1β and IL-6) and less lung damage in CLP-induced ARDS. Furthermore, recombinant IL-35 reduced the apoptosis of lung tissue and the expression of NF-κB signalling in a CLP-induced ARDS model and increased the proportion of Treg cells in spleen and peripheral blood. In vitro experiments revealed that IL-35 can affect the phosphorylation of STAT5 during differentiation of naïve CD4+ T lymphocytes into Foxp3+Helios+ Tregs. Our findings suggest that IL-35 attenuates ARDS by promoting the differentiation of naïve CD4+ T cells into Foxp3+Helios+ Tregs, thereby providing a novel tool for anti-ARDS therapy. [ABSTRACT FROM AUTHOR]

Disruption of Wnt signaling often happens in tumorigenesis, but whether Wnt signaling affects the early stages of thyroid tumor, such as papillary thyroid carcinoma, is still a question, especially in the papillary thyroid carcinoma without genomic RET/PTC mutation. In this study, we demonstrated the important function of Wnt signaling in papillary thyroid carcinoma K1 cells, which have no RET/PTC mutation. We found that K1 cells have enhanced Wnt signaling in comparison to normal thyroid cells. We further demonstrated that K1 cells require the enhanced Wnt signaling for growth and survival. Interestingly, we identified that enhancing E2F activity by either knockdown of Rb or overexpression of Cyclin D1 induces cell death in K1 cells. And we further revealed that the cell death is caused by enhanced oxidative stress. Our studies present a novel cell model to support the key roles of Wnt signaling in early stage of thyroid tumor, and also provide an alternative way to limit thyroid cancer. [ABSTRACT FROM AUTHOR]

To achieve the purpose of accurately grasping a random target with the upper limb prosthesis, the acquisition of target localization information is especially important. For this reason, a novel type of random target localization algorithm is proposed. Firstly, an initial localization algorithm (ILA) that uses two 3D attitude sensors and a laser range sensor to detect the target attitude and distance is presented. Secondly, an error correction algorithm where a multipopulation genetic algorithm (MPGA) optimizes backpropagation neural network (BPNN) is utilized to improve the accuracy of ILA. Thirdly, a general regression neural network (GRNN) algorithm is proposed to calculate the joint angles, which are used to control the upper limb prosthetic gripper to move to the target position. Finally, the proposed algorithm is applied to the 5-DOF upper limb prosthesis, and the simulations and experiments are proved to demonstrate the validity of the proposed localization algorithm and inverse kinematics (IK) algorithm. [ABSTRACT FROM AUTHOR]

A point cloud that is obtained by an RGB-D camera will inevitably be affected by outliers that do not belong to the surface of the object, which is due to the different viewing angles, light intensities, and reflective characteristics of the object surface and the limitations of the sensors. An effective and fast outlier removal method based on RGB-D information is proposed in this paper. This method aligns the color image to the depth image, and the color mapping image is converted to an HSV image. Then, the optimal segmentation threshold of the V image that is calculated by using the Otsu algorithm is applied to segment the color mapping image into a binary image, which is used to extract the valid point cloud from the original point cloud with outliers. The robustness of the proposed method to the noise types, light intensity and contrast is evaluated by using several experiments; additionally, the method is compared with other filtering methods and applied to independently developed foot scanning equipment. The experimental results show that the proposed method can remove all type of outliers quickly and effectively. [ABSTRACT FROM AUTHOR]

Background/Aim. We aimed to identify the differentially expressing metabolites (DEMs) in the muscles of the mouse model of sepsis-induced acquired weakness (sepsis-AW) using liquid chromatography-mass spectrometry (LC-MS). Materials and Methods. Sepsis by cecal ligation puncture (CLP) with lower limb immobilization was used to produce a sepsis-AW model. After this, the grip strength of the C57BL/6 male mice was investigated. The transmission electron microscopy was utilized to determine the pathological model. LC-MS was used to detect the metabolic profiles within the mouse muscles. Additionally, a statistically diversified analysis was carried out. Results. Compared to the sepsis group, 30 DEMs, including 17 upregulated and 13 down-regulated metabolites, were found in the sepsis-AW group. The enriched metabolic pathways including purine metabolism, valine/leucine/isoleucine biosynthesis, cGMP-PKG pathway, mTOR pathway, FoxO pathway, and PI3K-Akt pathway were found to differ between the two groups. The targeted metabolomics analysis explored significant differences between four amino acid metabolites (leucine, cysteine, tyrosine, and serine) and two energy metabolites (AMP and cAMP) in the muscles of the sepsis-AW experimental model group, which was comparable to the sepsis group. Conclusion. The present work identified DEMs and metabolism-related pathways within the muscles of the sepsis-AW mice, which offered valuable experimental data for diagnosis and identification of the pathogenic mechanism underlying sepsis-AW. [ABSTRACT FROM AUTHOR]

Different from traditional redundant manipulators, the redundant manipulators used in the surgical environment require the end effector (EE) to have high pose (position and orientation) accuracy to ensure the smooth progress of the operation. When analyzing the inverse kinematics (IK) of traditional redundant manipulators, gradient-projection method (GPM) and weighted least-norm (WLN) method are commonly used methods to avoid joint position limits. However, for the traditional GPM and WLN method, when joints are close to their limits, they stop moving, which greatly reduces the accuracy of the IK solution. When robotic manipulators enter a singular region, although traditional damped least-squares (DLS) algorithms are used to handle singularities effectively, motion errors of the EE will be introduced. Furthermore, selecting singular region through trial and error may cause some joint velocities exceed their corresponding limits. More importantly, traditional DLS algorithms cannot guide robotic manipulators away from singular regions. Inspired by the merits of GPM, WLN, and DLS methods, an improved weighted gradient projection method (IWGPM) is proposed to solve the IK problem of redundant manipulators used in the surgical environment with avoiding joint position limits and singularities. The weighted matrix of the WLN method and the damping factor of the DLS algorithm have been improved, and a joint limit repulsive potential field function and singular repulsive potential field function belong to the null space are introduced to completely keep joints away from the damping interval and redundant manipulators away from the unsafe region. To verify the validity of the proposed IWGPM, simulations on a 7 degree of freedom (DOF) redundant manipulator used in laparoscopic surgery indicate that the proposed method can not only achieve higher accuracy IK solution but also avoid joint position limits and singularities effectively by comparing them with the results of the traditional GPM and WLN method, respectively. Furthermore, based on the proposed IWGPM, simulation tests in two cases show that joint position limits have a great impact on the orientation accuracy, and singular potential energy function has a great impact on the position accuracy. [ABSTRACT FROM AUTHOR]

Fused deposition modeling (FDM) has the advantage of being able to process complex workpieces with relatively simple operations. However, when processing complex components in a suspended state, it is necessary to add support parts to be processed and formed, which indicates an excessive dependence on support. The stress intensity of the supported positions of the printing components can be modified by changing the supporting model of the parts, their density, and their distance in relation to the Z direction in the FDM printing settings. The focus of the present work was to study the influences of these three modified factors on the stress intensity of the supporting position of the printing components. In this study, 99 sets of compression tests were carried out using a position of an FDM-supported part, and the experimental results were observed and analyzed with a 3D topographic imager. A reference experiment on the anti-pressure abilities of the printing components without support was also conducted. The experimental results clarify how the above factors can affect the anti-pressure abilities of the supporting positions of the printing components. According to the results, when the supporting density is 30% and the supporting distance in the Z direction is Z = 0.14, the compressive strength of the printing component is lowest. When the supporting density of the printing component is ≤30% and the supporting distance in the Z direction is Z ≥ 0.10, the compressive strength of printing without support is greater than that of the linear support model. Under the same conditions, the grid-support method offers the highest compressive strength. [ABSTRACT FROM AUTHOR]

Background. Basil polysaccharide (BPS) represents a main active ingredient extracted from basil (Ocimum basilicum L.), which can regulate secondary bacterial pneumonia development in the process of sepsis-mediated immunosuppression. Methods. In this study, a dual model of sepsis-induced secondary pneumonia with cecal ligation and puncture and intratracheal instillation of Staphylococcus aureus or Pseudomonas aeruginosa was constructed. Results. The results indicated that BPS-treated mice undergoing CLP showed resistance to secondary S. aureus pneumonia. Compared with the IgG-treated group, BPS-treated mice exhibited better survival rate along with a higher bacterial clearance rate. Additionally, BPS treatment attenuated cell apoptosis, enhanced lymphocyte and macrophage recruitment to the lung, promoted pulmonary cytokine production, and significantly enhanced CC receptor ligand 4 (CCL4). Notably, recombinant CCL4 protein could enhance the protective effect on S. aureus-induced secondary pulmonary infection of septic mice, which indicated that BPS-induced CCL4 partially mediated resistance to secondary bacterial pneumonia. In addition, BPS priming markedly promoted the phagocytosis of alveolar macrophages while killing S. aureus in vitro, which was related to the enhanced p38MAPK signal transduction pathway activation. Moreover, BPS also played a protective role in sepsis-induced secondary S. aureus pneumonia by inducing Treg cell differentiation. Conclusions. Collectively, these results shed novel lights on the BPS treatment mechanism in sepsis-induced secondary S. aureus pneumonia in mice. [ABSTRACT FROM AUTHOR]

Background. Sepsis-associated encephalopathy (SAE) is a transient and reversible brain dysfunction, that occurs when the source of sepsis is located outside of the central nervous system; SAE affects nearly 30% of septic patients at admission and is a risk factor for mortality. In our study, we sought to determine whether metabolite changes in plasma could be a potential biomarker for the early diagnosis and/or the prediction of the prognosis of sepsis. Method. A total of 31 SAE patients and 28 healthy controls matched by age, gender, and body mass index (BMI) participated in our study. SAE patients were divided into four groups according to the Glasgow Coma Score (GCS). Plasma samples were collected and used to detect metabolism changes by gas chromatography-mass spectrometry (GC-MS). Analysis of variance was used to determine which metabolites significantly differed between the control and SAE groups. Results. We identified a total of 63 metabolites that showed significant differences among the SAE and control groups. In particular, the 4 common metabolites in the four groups were 4-hydroxyphenylacetic acid; carbostyril, 3-ethyl-4,7-dimethoxy (35.8%); malic acid peak 1; and oxalic acid. The concentration of 4-hydroxyphenylacetic acid in sepsis patients decreased with a decrease of the GCS. Conclusions. According to recent research on SAE, metabolic disturbances in tissue and cells may be the main pathophysiology of this condition. In our study, we found a correlation between the concentration of 4-hydroxyphenylacetic acid and the severity of consciousness disorders. We suggest that 4-hydroxyphenylacetic acid may be a potential biomarker for SAE and useful in predicting patient prognosis. [ABSTRACT FROM AUTHOR]

Metrnl play an immunocytokine-like role in several diseases, which is also known as meteorin-like because it is homologous to the neurotrophic factor meteorin (Metrn). Although the expression and function of Metrnl, including neurotrophic, immunomodulatory, and insulin resistance functions in different tissues have been extensively studied, its role in sepsis has remained largely limited. The present work analyzed the levels of Metrnl and cytokines in the circulation, such as tumor necrosis factor (TNF-α), interleukin (IL-1)β, IL-6, IL-8, together with IL-10 among septic adult patients. Clinical information was obtained from such patients, including sofa score, procalcitonin(PCT)count, and C-reactive count (CRP) within 24 h when entering the intensive care unit (ICU). We constructed a sepsis model in Metrnl-deficient or normal wild-type mice using cecal ligation and perforation to study its functions in bacterial burden, survival, cytokine/chemokine generation, peritoneal lavage fluid neutrophils, macrophage and lymphocyte recruitment, and Treg/Th17 immune cell balance after CLP-induced sepsis. The expression of Metrnl was remarkably elevated in the early phase of sepsis clinically. Its serum content in patients dying of sepsis slightly decreased relative to that in survivors. Furthermore, the concentration of Metrnl in septic cases when entering the ICU independently predicted the 28-day mortality. For septic patients who had low serum Metrnl content (≤ 274.40 pg/mL), the death risk increased by 2.3 folds relative to those who had a high serum content. It is reported that Metrnl is probably insufficient among patients dying of sepsis. Additionally, the content of Metrnl in the serum of septic patients when entering the ICU is markedly and negatively related to the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17, PCT, and Sofa score. Collectively, Metrnl could be a potential therapeutic target for sepsis. A low-lethality non-severe sepsis (NSS) model was constructed, which suggested that Metrnl insufficiency elevated the death rate and reduced bacterial clearance during sepsis. For Metrnl-deficient mice, impaired sepsis immunity defense might be related to decreased macrophage recruitment and Treg/Th17 lymphocyte imbalance. Recombinant Metrnl administered to Metrnl-deficient mice abolished the immunity defense impairment following NSS while protecting the high-lethality severe sepsis (SS) model in wild-type (WT) mice. In addition, Metrnl-induced sepsis prevention was intricately associated with the increased recruitment of peritoneal macrophages and modulation of the Treg/TH17 immune cell balance. Furthermore, CCL3 exposure in Metrnl-deficient mice reduced peritoneal bacterial loads while improving survival during sepsis partially by promoting the recruitment of peritoneal macrophages. Furthermore, Metrnl regulated the polarization of M1 macrophages through the ROS signaling pathway and promoted macrophage phagocytosis, thereby killing Escherichia coli. The present proof-of-concept work suggests that Metrnl-mediated recruitment of macrophages significantly affects sepsis defense in the host and modulates the Treg/Th17 immune cell balance. Findings in this work shed more light on the development of host-directed treatments that can be used to manipulate host immunity to treat sepsis. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to analyse the metabolomics of patients with acute respiratory distress syndrome (ARDS) for the identification of metabolic markers with potential diagnostic and prognostic value. Methods The enrolled subjects included adult patients with ARDS that met the Berlin definition and healthy controls matched based on age, gender, and body mass index (BMI). Plasma samples were collected from 37 patients with ARDS and 28 healthy controls. The plasma metabolites were detected with gas chromatography–mass spectrometry (GC–MS), and the relevant metabolic pathways were predicted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results A total of 222 metabolites were identified in our study, of which 128 were significantly altered in patients with ARDS compared with healthy controls. Phenylalanine, aspartic acid, and carbamic acid levels were significantly different between all groups of patients with ARDS classified from mild to severe. Furthermore, four metabolites, ornithine, caprylic acid, azetidine, and iminodiacetic acid, could serve as biomarkers to potentially predict the severity of ARDS. We discovered 92 pathways that were significantly different between ARDS and control groups, including 57 pathways linked to metabolism. Conclusions Plasma metabolomics may improve our understanding of ARDS biology. Specific products related to hypoxia may serve as early biomarkers for ARDS prediction, while the metabolites with significant correlations with partial pressure of arterial oxygen (PaO 2)/percentage of inspired oxygen (FiO 2) may play a role in determining ARDS severity. This study suggests that metabolomic analysis in patients at risk of ARDS or those with early ARDS may provide new insight into disease pathogenesis or prognosis. [ABSTRACT FROM AUTHOR]

Background: Interleukin 38 (IL-38) is the most recently characterized cytokine of the interleukin 1 family. However, its role in sepsis remains unknown.Methods: Circulating IL-38 levels were measured in 2 cohorts of adult and pediatric patients with sepsis. Using 2 murine models of lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, and bacterial clearance were assessed.Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively. An increased IL-38 level negatively correlated with the number of blood leukocytes and with the level of inflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in clinical sepsis. Anti-IL-38 antibody impaired survival and while recombinant IL-38 improved survival in the 2 murine models of LPS-induced endotoxemia and CLP-induced sepsis. IL-38 administration decreased the inflammatory response, as reflected by lower levels of cytokines and chemokines (including IL-6, TNF-α, interleukin 10, interleukin 17, interleukin 27, CXCL1, and CCL2), and less damage to tissues (including lung, liver, and kidney) in CLP-induced sepsis. Furthermore, IL-38 augmented bacterial clearance in CLP-induced polymicrobial sepsis.Conclusions: These findings suggest that IL-38 attenuates sepsis by decreasing inflammation and increasing bacterial clearance, thus providing a novel tool for antisepsis therapy. [ABSTRACT FROM AUTHOR]

Background: Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36α (IL-36α) in host response during sepsis remains unknown.Methods: An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36α on host response to sepsis.Results: IL-36α production was significantly up-regulated during sepsis. IL-36α treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36α-treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36α led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36α enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36α-mediated protection against sepsis.Conclusions: Our results demonstrate that IL-36α plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36α in sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Phlegmasia cerulea dolens is a rare condition caused by complete venous occlusion leading to impaired arterial flow. To prevent progression to limb gangrene, prompt diagnosis and treatment initiation are paramount. Here we report a rare case of posttraumatic phlegmasia cerulea dolens after ligation of the iliac vein to save the patient's life, with successful treatment by reconstructing the external iliac vein. This is the first report of posttraumatic phlegmasia cerulea dolens induced by iliac vein ligation.Case Presentation: A 49-year-old Chinese man was admitted to a local hospital for severe knife trauma with massive intraperitoneal bleeding. During exploratory laparotomy, he was diagnosed with traumatic rupture of his left external iliac vein without injury to the iliac artery. The proximal and distal parts of his injured external iliac vein were ligated to control the bleeding and rescue him, but his left leg quickly became severe swollen, cyanotic and pulseless. He was diagnosed with posttraumatic phlegmasia cerulea dolens after being transferred to our university hospital. After a retrievable filter was placed in his inferior vena cava via his right femoral vein, he underwent reopening of his abdomen followed by successful surgical reconstruction of his left iliac vein. He was treated with anticoagulation therapy postoperatively and his signs and symptoms improved markedly. He was discharged in a stable condition, with nearly full resolution of symptoms, 35 days after the operation.Conclusions: Our case demonstrates that ligation of an injured iliac vein may induce phlegmasia cerulea dolens in a posttraumatic scenario; prompt reconstruction of the iliac vein to restore the venous drainage is an effective treatment for phlegmasia cerulea dolens with impending gangrene. [ABSTRACT FROM AUTHOR]

Fractalkine, CX3CL1, is involved in the directional movement of chemokine cells, immune response, inflammatory response, tissue repair, and other processes. However, its role in sepsis is not well known. We measured circulating Fractalkine in adult patients with sepsis. Effects of Fractalkine on the survival, inflammation, tissue injury, and bacterial clearance were assessed using the WT or CX3CL−/− murine model of cecal ligation and puncture (CLP)-induced sepsis. Serum Fractalkine concentrations were significantly elevated in adult patients with sepsis compared to healthy adults. Increased Fractalkine correlated positively with the number of blood leukocytes and the level of inflammatory cytokines, including IL-6, IL-1β, IL-17A, IFN-γ, and TNF-α, and correlated negatively with IL-10 in clinical sepsis. Recombinant Fractalkine impaired survival whereas Fractalkine gene knockout or anti-Fractalkine antibody improved survival in the murine model of CLP-induced sepsis. Fractalkine administration increased inflammatory response, evident by higher levels of cytokines (TNF-α, IL-1β, IL-17A, IFN-γ, and IL-6 but not IL-10), and tissue damage (lung, liver, and kidney) in CLP-induced sepsis. Fractalkine reduced bacterial clearance in CLP-induced polymicrobial sepsis by reducing macrophage or neutrophil phagocytosis and intracellular elimination of E. coli. Fractalkine aggravates sepsis by increasing inflammation and decreasing bacterial clearance, and is a potential tool for anti-sepsis therapy. • FKN release occurred in clinical sepsis. Elevated FKN has a potential pro-inflammatory effect in in clinical sepsis. • FKN exacerbated experimental sepsis by increasing inflammatory responses and reducing the bacterial removal. • FKN weakened the ability of macrophages and neutrophils to engulf and eliminate E. coli. [ABSTRACT FROM AUTHOR]