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Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage‐related genes in DFU and identify possible therapeutic targets. Single‐cell datasets (GSE223964) and RNA‐seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single‐cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA‐seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and Western bolt. Finally, the findings were validated using RT‐qPCR and western blot. We obtained 802 macrophage‐related genes in single‐cell analysis. Differential expression analysis yielded 743 DEGs. Thirty‐seven macrophage‐associated DEGs were identified by cross‐analysis of marker genes with macrophage‐associated DEGs. Thirty‐seven intersections were screened and cross‐analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU. [ABSTRACT FROM AUTHOR]

Objective. Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). Methods. This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. Results. All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 μg/ml. Conclusions. Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI. [ABSTRACT FROM AUTHOR]

This study investigated potential imaging biomarkers for predicting the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). A total of 59 PD patients and 50 healthy control subjects underwent high-resolution 3-dimensional T1-weighted brain magnetic resonance imaging. Bilateral STN volumes were compared between the 2 groups, and a correlation analysis was performed to assess the relationship between bilateral STN volumes or intracranial volume (ICV) and pre- or postoperative clinical scale scores. The results showed that the left STN volume differed significantly between PD patients and controls. In patients, the left STN volume was negatively correlated with pre- and postoperative quality of life scores and positively correlated with Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment scores; ICV was also positively correlated with the MMSE score. These findings indicate that changes in the left STN volume are a useful biomarker for evaluating the clinical outcome of PD patients following DBS. [ABSTRACT FROM AUTHOR]

Objective. Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. Methods. In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. Results. A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups (p > 0.05). Compared with the NC group, the SCI group had a higher serum CCL21 level (p < 0.001) and a lower MoCA score (p < 0.001). Serum CCL21 level in SCI was negatively correlated with MoCA score (p = 0.023). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. Conclusions. MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI. [ABSTRACT FROM AUTHOR]

Objective. Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. Methods. All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. Results. A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = − 0.327 , p < 0.05). Conclusion. The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI. [ABSTRACT FROM AUTHOR]

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3β (GSK-3β) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3β activity and expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3β inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3β, and increased IL-1β and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3β signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits. [ABSTRACT FROM AUTHOR]

A rice male-sterile mutant OsMS-L of japonica cultivar 9522 background, was obtained in M4 population treated with 60Co γ-Ray. Genetic analysis indicated that the male-sterile phenotype was controlled by a single recessive gene. Results of tissue section showed that at microspore stage, OsMS-L tapetum was retarded. Then tapetal cells expanded and microspores degenerated. No matured pollens were observed in OsMS-L anther locus. To map OsMS-L locus, an F2 population was constructed from the cross between the OsMS-L (japonica) and LongTeFu B(indica). Firstly, the OsMS-L locus was roughly mapped between two SSR markers, RM1O9 and RM7562 on chromosome 2. And then eleven polymorphic markers were developed for further fine fine-mapping. At last the OsMS-L locus was mapped between the two InDel markers, Lbs 10 and Lhs6 with genetic distance of 0.4 cM, respectively. The region was delimited to 133 kb. All these results were useful for further cloning and functional analysis of OsMS-L. [ABSTRACT FROM AUTHOR]

Cellular senescence is a well-established model system for studying the molecular basis of aging. To identify a reliable biomarker for cellular age and further study the gene expression of aging, we profiled the gene expression difference between aged and young cultured human embryonic lung fibroblasts by high-density complementary deoxyribonucleic acid (cDNA) arrays. Among the differentially expressed genes, alpha-2-macroglobulin (α2M) was selected for further study. Its gene expression level as a function of population doubling level (PDL) in cultured fibroblasts was determined by RT-PCR and northern hybridization. mRNA level of α2M showed a positive linear-correlation with cumulative PDL. Additional assays revealed that the levels of α2M increased in irreversible growth arrest induced by sublethal H2O2, but not in quiescent state of cultured fibroblasts induced by serum-deprivation, and remained stable in Hela cells. These results suggest that mRNA level of α2M can be used as a biomarker of aging in cultured fibroblasts. mRNA level of α2M showed significant difference between newborn and old human leucocytes, which suggest that the mRNA level of α2M may be used as a biomarker of aging in vivo. [Copyright &y& Elsevier]

Heroin, drug abuse, biomarker, plasma microRNA, addiction Keywords: heroin; drug abuse; biomarker; plasma microRNA; addiction EN heroin drug abuse biomarker plasma microRNA addiction 1 1 1 07/28/21 20210726 NES 210726 In the published article, there was an error in the affiliations and equal contributions in the author list. Publisher's Note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. [Extracted from the article]

Targeted proteomics has advantages over earlier conventional technologies for protein detection. We developed and validated an LC/MRM-MS-based targeted proteomic method combined with immunoaffinity precipitation for the enrichment and detection of low abundance chemerin isoforms in human biofluids. After tryptic digestion, each chemerin isoform was characterized by isoform-specific peptides, and the absolute quantification was achieved by using stable isotope-labeled peptides as internal standards. In serum, follicular fluid and synovial fluid, a total of 6 chemerin isoforms were identified and quantified, among which a novel natural isoform 153Q was discovered for the first time. The relative content of the six chemerin isoforms in human serum was 157S ≫ 156F ≫ 158K > 154F ≥ 155A > 153Q in the ratio of 25:17:5:2.5:2.2:1, respectively. The absolute contents were in the range of 88–3.5 ng/mL. This distribution remained consistent among the 3 biofluids analyzed. Total chemerin were found to be increased in both polycystic ovary syndrome (serum and follicular fluid) and rheumatoid arthritis (serum) patients. However, chemerin isoform analysis revealed that only 156F & 157S were increased in the former, while 155A, 156F & 157S were increased in the latter. This demonstrates the potential of this method in detailed characterization of changes in chemerin isoforms that may be of clinical relevance. Image 1 • Chemerin protein was analyzed by LC/MRM-MS-based targeted proteomics approach. • Immunoaffinity purification and Stable Isotope-labeled Standard have been employed. • Six isoforms including a new 153Q of chemerin have been analyzed in human biofluids. • The levels of several specific isoforms may be associated with PCOS or RA. [ABSTRACT FROM AUTHOR]

Background and Objectives: Obesity is linked to metabolic diseases characterized by insulin resistance, such as diabetes and cardiovascular disease. In this study, we investigated the metabolic disorders of uncomplicated obesity to identify early alterations in biological systems.Methods and Study Design: Metabolic differences between overweight/obese (n=36) and normal-weight (n=35) young Chinese men without known metabolic disorders were assessed. Metabolic profiling of the serum and urine was performed using ultra-performance liquidchromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminant analysis (PLS-DA) was undertaken to reveal and classify the differences between the two groups.Results: Compared to normal-weight men, obese men had higher levels of the serum metabolites phenylalanine, Phe-Phe, and L-tryptophan, whereas those of p-cresol sulfate and p-cresol were less in obesity. Urinary metabolites phenylacetamide, L-glutamine, phenylacetylglutamine, indoxyl sulfate, p-cresol, and p-cresol sulfate were greater in obese men.Conclusions: These findings indicate that disorders involving aromatic amino acids and the tricarboxylic acid cycle (TCA) have microbiomic involvement in the uncomplicated phase of obesity. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. 20 potential diagnostic biomarkers were selected. Moreover, 9 metabolites were found to be closely correlated with the pathological feature such as local invasion, lymphatic metastasis and postoperative survival time. Glutamate was correlated with local invasion of tumor, and oleic acid, LysoPC(15:0), uracil, inosine and choline were closely related with the lymphatic metastasis, while glutamine, kynurenine, serine and uracil were related with postoperative survival time. The results indicated that the potential biomarkers discovered by metabolomics could reflect the metabolic characterization of ESCC, and offers a novel approach for early diagnosis, assessment and prognosis of the disease. [ABSTRACT FROM AUTHOR]