Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their ...filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques. Compared with healthy controls, patients with CKD showed activation of NF-κB and up-regulation of pro-inflammatory and pro-oxidant mRNA and protein expression as well as down-regulation of Nrf2-associated anti-oxidant gene mRNA and protein expression, accompanied by activated canonical Wnt/β-catenin signaling. 124 plasma and 128 urine metabolites were identified and 40 metabolites were significantly altered in both plasma and urine. Plasma concentration and urine excretion of 25 metabolites were distinctly different between CKD and controls. They were related to amino acid, methylamine, purine and lipid metabolisms. Logistic regression identified four plasma and five urine metabolites. Parts of them were good correlated with eGFR or serum creatinine. 5-Methoxytryptophan and homocystine and citrulline were good correlated with both eGFR and creatinine. Clinical factors were incorporated to establish predictive models. The enhanced metabolite model showed 5-methoxytryptophan, homocystine and citrulline have satisfactory accuracy, sensitivity and specificity for predictive CKD. The dysregulation of CKD was related to amino acid, methylamine, purine and lipid metabolisms. 5-methoxytryptophan, homocystine and citrulline could be considered as additional GFR-associated biomarker candidates and for indicating advanced renal injury. CKD caused dysregulation of the plasma and urine metabolome, activation of inflammatory/oxidative pathway and Wnt/β-catenin signaling and suppression of antioxidant pathway.
Regulatory T Cells in GVHD Therapy Guo, Wen-wen; Su, Xiu-hua; Wang, Ming-yang ...
Frontiers in immunology,
06/2021, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
Graft
versus
host disease (GVHD) is a common complication and the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Pharmacological ...immunosuppression used in GVHD prophylaxis and treatment lacks specificity and can increase the likelihood of infection and relapse. Regulatory T lymphocytes (Tregs) play a vital role in restraining excessive immune responses and inducing peripheral immune tolerance. In particular, clinical trials have demonstrated that Tregs can prevent and treat GVHD, without increasing the risk of relapse and infection. Hence, adoptive transfer of Tregs to control GVHD using their immunosuppressive properties represents a promising therapeutic approach. To optimally apply Tregs for control of GVHD, a thorough understanding of their biology is necessary. In this review, we describe the biological characteristics of Tregs, including how the stability of FOXP3 expression can be maintained. We will also discuss the mechanisms underlying Tregs-mediated modulation of GVHD and approaches to effectively increase Tregs’ numbers. Finally, we will examine the developing trends in the use of Tregs for clinical therapy.
Abstract
Objective
this retrospective study aims to compare the prevalence and diagnostic agreement of sarcopenic obesity (SO) using different obesity diagnostic methods among Chinese ...community-dwelling older adults.
Methods
SO was diagnosed with sarcopenia and obesity diagnostic methods. Sarcopenia was defined using the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019). Four widely used indicators were used to define obesity: body mass index (BMI), waist circumference (WC), percent of body fat (PBF) and visceral fat area (VFA). Cohen’s kappa was used to analyse the diagnosis agreement of SO between different diagnostic methods.
Results
a total of 1,050 participants were included, including 347 men (71.3 ± 7.4 years) and 703 women (69.9 ± 7.5 years). The prevalence of sarcopenia was 25% in total participants, there was no difference between men (24.2%) and women (25.5%), (P = 0.705). With different obesity diagnostic methods, the obesity prevalence ranged from 4.1 to 42.2%, the SO prevalence was 0.1–7.9%. The diagnosis agreement of SO was poor-to-moderate (κ ranged from −0.002 to 0.682). Among the four diagnostic methods, AWGS combined with BMI had the poorest agreement (κ = −0.002 with other methods), AWGS combined with VFA had the best agreement (κ = 0.641 and 0.682 with AWGS combined with PBF and with AWGS combined with WC, respectively).
Conclusion
the prevalence of SO vary considerably and the diagnostic agreement is poor-to-moderate with non-uniform diagnostic methods. BMI has the lowest sensitivity, whereas VFA has the highest sensitivity in diagnosis of SO, and VFA has a relatively good diagnostic agreement with other diagnostic methods.
We propose a decent synergetic effect produced by delicate hybridization between exfoliated MoSe2 nanosheets and high conductive Ag nanoparticles during self-assemble process. Uniformly dispersed Ag ...NPs on MoSe2 nanosheets would accelerate electrons transfer as well as efficiently inhabit the stack of MoSe2 nanosheets, exposing more active edge sites to enhance electrocatalytic activity on hydrogen reduction as well as facilitate electrochemical storage of lithium ions.
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•Controllable construction of Ag/MoSe2 hybrid architectures.•The homogeneous decorated Ag NPs can greatly improve the conductivity of MoSe2 nanosheets.•MoSe2 nanosheets buffer the volume variation during repeated lithium ions insertion and extraction process.•Ag/MoSe2 hybrid architectures exhibited stronger HER and lithium storage property.
Tradition metal selenides have triggered extensive attentions in the field of electrochemical energy storage and conversion. Herein we propose a decent synergetic effect produced by delicate hybridization between exfoliated MoSe2 nanosheets and high conductive Ag nanoparticles (NPs) during self-assemble process. The Ag/MoSe2 hybrid architecture (weight ratio, 5:100) can reach 10 mA cm−2 current density at a potential as low as 0.187 V, which almost is ~3-fold lower than that for the bare MoSe2 nanosheets. Additionally, the Ag/MoSe2 hybrid architecture also exhibits an enhanced capacity, excellent rate abilities and superior cycling stability for lithium storage than pristine MoSe2 nanosheets. The comprehensive explorations of the synergistic effects occurring between MoSe2 nanosheets and Ag NPs have insights for the rational constructions of low cost electrocatalysts for hydrogen evolution as well as high performance electrode materials for lithium storage based on transition metal chalcogenides.
To establish and validate a nomogram that predicts the risk of sarcopenia for community-dwelling older residents.
Retrospective study.
A total of 1050 community-dwelling older adults.
Data from a ...survey of community-dwelling older residents (≥60 years old) in Hunan, China, from June to September 2019 were retrospectively analyzed. The survey included general demographic information, diet, and exercise habits. Sarcopenia diagnosis was according to 2019 Asian Working Group for Sarcopenia criteria. Participants were randomly divided into the development group and validation groups. Independent risk factors were screened by multivariate logistic regression analysis. Based on the independent risk factors, a nomogram model was developed to predict the risk of sarcopenia for community-dwelling older adults. Both in the development and validation sets, the discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic curve analysis, Hosmer-Lemeshow test, and decision curve analysis, respectively.
Sarcopenia was identified in 263 (25.0%) participants. Age, body mass index, marital status, regular physical activity habit, uninterrupted sedentary time, and dietary diversity score were significant contributors to sarcopenia risk. A nomogram for predicting sarcopenia in community-dwelling older adults was developed using these factors. Receiver operating characteristic curve analysis showed that the area under the curve was 0.827 (95% CI 0.792-0.860) and 0.755 (95% CI 0.680-0.837) in the development and validation sets, respectively. The Hosmer-Lemeshow test yielded P values of .609 and .565, respectively, for the 2 sets. The nomogram demonstrated a high net benefit in the clinical decision curve in both sets.
This study developed and validated a risk prediction nomogram for sarcopenia among community-dwelling older adults. Sarcopenia risk was classified as low (<11%), moderate (11%-70%), and high (>70%). This nomogram provides an accurate visual tool to medical staff, caregivers, and older adults for prediction, early intervention, and graded management of sarcopenia.
Girdin is a downstream effector of epidermal growth factor receptor (EGFR)‐AKT and interacts with actin and microtubule. Increasing evidence confirmed that Girdin played an important role in cell ...migration. Here we report that Girdin also regulates cell division. Overexpression or suppression of Girdin leads to attenuated cell proliferation. Imaging of mitotic cells revealed that Girdin is located in the cell division apparatus such as centrosome and midbody. The sub‐cellular localization of Girdin was dependent on the domains, which interacted with actin or microtubules. Overexpression of Girdin lead to increased centrosome splitting and amplification. In addition, data show that pAKT also locates in both the centrosome and midbody, indicating the regulating role of AKT in Girdin‐mediated cell division. To elucidate the effect of Girdin on tumor growth in vivo, HeLa cells infected with retrovirus harboring either control or Girdin shRNAs were injected subcutaneously into the immunocompromised nude mice. Downregulation of Girdin by shRNA markedly inhibited the cell growth of subcutaneously transplanted tumors in nude mice. These data demonstrate that Girdin is important for efficient cell division. Taking our previous data into consideration, we speculate that Girdin regulates both cell division and cell migration through cytoskeletal molecules.
Summary
Aims
To explore risk factors for stroke independent of hypertension and the relationship between riboflavin kinase (RFK) and stroke.
Methods
Gene expression profiling in the brains of ...spontaneously hypertensive rats (SHR) and stroke‐prone spontaneously hypertensive rats (SHRSP) was comparatively analyzed by gene chips. The differentially expressed gene RFK was further verified by q‐PCR and Western blot. The protective role of RFK‐regulated flavins (including riboflavin, flavin mononucleotide, and flavin adenine dinucleotide) in stroke was observed in middle cerebral artery occlusion (MCAO) mice. Influence of flavins on apoptosis and death in oxygen and glucose deprivation (OGD)‐treated neurons was examined by flow cytometry. Bax and Bcl‐2 proteins were detected by Western blot.
Results
Of the 76 differentially expressed genes, 41 genes were upregulated, and 35 genes were downregulated in SHRSP as compared with SHR. RFK was significantly downregulated in SHRSP. Flavins markedly decreased infarct area in MCAO mice, inhibited apoptosis and death in OGD‐treated neurons, and decreased Bax protein expression.
Conclusions
Physiological downregulation of RFK may be a new potential risk factor for stroke, which probably affects the absorbance and utility of riboflavin and further destroys the protective effect of flavins on stroke. RFK might act as a therapeutic target for stroke.
Chitinase-3-like-1 protein (YKL-40), a member of the mammalian chitinase-like glycoproteins, serves a key role in the pathogenesis of rectal cancer. The present study examined the antitumor effect of ...theophylline, a pan-chitinase inhibitor, in rectal cancer
and investigated the mechanism by which it acted. SW480 cell lines were treated with varying theophylline concentrations (10
, 10
, 10
and 10
mol/l). An MTT assay was used to observe cell proliferation and identify the optimal theophylline concentration. Western blotting was used to analyze YKL-40 expression. The cell cycle distribution of SW480 cell lines treated with theophylline was measured by flow cytometry. The angiopoietin-2 expression level was measured by ELISA. The expression levels of YKL-40 were evidently decreased in theophylline-treated SW480 cell lines. The proliferation of SW480 cells was inhibited following theophylline treatment, which was associated with G
phase cell cycle arrest and a decrease in the expression of angiopoietin-2. The mechanism of theophylline action may involve the downregulation of YKL-40 expression, arrest of the cell cycle at G
phase and inhibition of angiopoietin-2 expression. These results provide a rationale for the potential use of anti-YKL-40 and anti-angiogenic strategies in treating rectal cancer.
SUMMARY
Aims: To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke‐prone spontaneously hypertensive rats (SHR‐SP). Methods: The ...differentially expressed brain protein profile was examined in spontaneously hypertensive rats (SHR) (control group) and SHR‐SP using two‐dimensional fluorescent difference gel electrophoresis (2D‐DIGE). In addition, oxidative stress indicators including total antioxidation capacity (TAC), glutathione peroxidase (GPx) activity, and maleic dialdehyde (MDA) were also measured. Lastly, SHR‐SP were randomly divided into untreated and treated (vitamins C (200 mg/kg/day) and E (100 mg/kg/day)) groups. After treatment for 4 weeks, half of the animals were sacrificed for detection of TAC, GPx, and MDA. The remaining rats underwent middle cerebral artery occlusion (MCAO) and the infarct areas were measured. Results: Compared with SHR, the infarct area of SHR‐SP was larger (P < 0.01), and the antioxidative proteins including glutathione S‐transferase (GST) Pi2 and GST A5 were lower; TAC and GPx activities were decreased and MDA levels. Treatment with vitamins C and E decreased MDA, and increased TAC and GPx activity significantly in SHR‐SP, while also decreasing the infarct area (P < 0.01). Conclusions: Our findings indicate that oxidative stress plays an important role in the pathogenesis of cerebral ischemia.
The energy-storage flywheel system has been becoming a kind of energy storage device with broad application prospect. It has the advantages of high energy storage density, high power, high ...efficiency, short charging time, long life, etc. In order to prevent energy storage flywheel system components deformation or failure under high speed, the static characteristic analyses on the flywheel rotor were done respectively under two types of the permanent magnet don't act on the rotor internal wall and the permanent magnet acts on the rotor internal wall, the deformation, equivalent stress, tangential stress, radial stress of the rotor were researched. The work can provides certain reference for the structure design, optimization design of the flywheel system.
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