Lactylation prediction models based on protein sequence and structural feature fusion.

Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.

Global profiling of protein lactylation in Caenorhabditis elegans.

Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota.

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.

[Identification of Protein-Coding Gene Markers in Breast Invasive Carcinoma Based on Machine Learning].

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Global profiling of lysine lactylation in human lungs.

Lactate is closely related to various cellular processes, such as angiogenesis, responses to hypoxia, and macrophage polarization, while regulating natural immune signaling pathways and promoting neurogenesis and cognitive function. Lysine lactylation (Kla) is a novel posttranslational modification, the examination of which may lead to new understanding of the nonmetabolic functions of lactate and the various physiological and pathological processes in which lactate is involved, such as infection, tumorigenesis and tumor development. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), researchers have identified lactylation in human gastric cancer cells and some other species, but no research on lactylation in human lungs has been reported. In this study, we performed global profiling of lactylation in human lungs under normal physiological conditions, and 724 Kla sites in 451 proteins were identified. After comparing the identified proteins with those reported in human lactylation datasets, 141 proteins that undergo lactylation were identified for the first time in this study. Our work expands the database on human lactylation and helps advance the study on lactylation function and regulation under physiological and pathological conditions.

Global analysis of lysine acetylation in the brain cortex of K18-hACE2 mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected hundreds of millions of people all over the world and thus threatens human life. Clinical evidence shows that SARS-CoV-2 infection can cause several neurological consequences, but the existing antiviral drugs and vaccines have failed to stop its spread. Therefore, an understanding of the response to SARS-CoV-2 infection of hosts is vital to find a resultful therapy. Here, we employed a K18-hACE2 mouse infection model and LC-MS/MS to systematically evaluate the acetylomes of brain cortexes in the presence and absence of SARS-CoV-2 infection. Using a label-free strategy, 3829 lysine acetylation (Kac) sites in 1735 histone and nonhistone proteins were identified. Bioinformatics analyses indicated that SARS-CoV-2 infection might lead to neurological consequences via acetylation or deacetylation of important proteins. According to a previous study, we found 26 SARS-CoV-2 proteins interacted with 61 differentially expressed acetylated proteins with high confidence and identified one acetylated SARS-CoV-2 protein nucleocapsid phosphoprotein. We greatly expanded the known set of acetylated proteins and provide the first report of the brain cortex acetylome in this model and thus a theoretical basis for future research on the pathological mechanisms and therapies of neurological consequences after SARS-CoV-2 infection.

Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.

BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC. METHODS: Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway. RESULTS: A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC. CONCLUSIONS: There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.

Detection of the freshness of rice by chemiluminescence.

Reactive oxygen species (ROS) are usually produced in rice under aerobic environmental conditions, resulting in peroxidative changes in polyunsaturated fatty acids, and affecting the deterioration of rice during storage. In addition, as an important enzyme that participates in removing ROS, peroxidase is also present in rice, and takes part in protecting rice from attack by ROS. Moreover, loss of peroxidase activity may give rise to rice deterioration during storage. Therefore, measuring peroxidase activity makes it possible to ascertain the freshness of rice. In addition, peroxidase can also catalyze the luminol-hydrogen peroxide system. Based on this, in this work we established a new chemiluminescence (CL) method that was used to detect the freshness of stored rice. Under optimal experimental conditions, we showed that the freshness of rice can be measured using this CL method. This study is the first to detect the freshness of rice using a CL method, opening up a novel direction for the application of CL.

[Role of Eukaryotic Translation Elongation Factor 1 Family Members in the Tumorigenesis and Progression of Lung Adenocarcinoma].

Objective To investigate the role and mechanism of eukaryotic translation elongation factor 1(EEF1) family members (EEF1D,EEF1A1,and EEF1A2) in lung adenocarcinoma (LUAD) based on public databases.Methods We examined EEF1 member expression levels in human LUAD samples via The Cancer Genome Atlas in the UCSC Xena browser and the Clinical Proteomic Tumor Analysis Consortium.We analyzed the mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 and their correlations with pathological variables via the Mann-Whitney U test.The Kaplan-Meier curves were established to assess the prognostic values of EEF1D,EEF1A1,and EEF1A2.The single-sample gene set enrichment analysis algorithm was employed to explore the relationship between the expression levels of EEF1 members and tumor immune cell infiltration.Spearman and Pearson correlation analyses were performed to examine the relationship between the expression levels of EEF1 members and those of the genes in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.The immunohistochemical assay was employed to determine the expression levels of EEF1D,EEF1A1,and EEF1A2 in the LUAD tissue (n=75) and paracancer tissue (n=75) samples.Results The mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 showed significant differences between tumor and paracancer tissues (all P<0.001).The patients with high protein levels of EEF1A1 showed bad prognosis in terms of overall survival (P=0.039),and those with high protein levels of EEF1A2 showed good prognosis in terms of overall survival (P=0.012).The influence of the mRNA level of EEF1D on prognosis was associated with pathological characteristics.The expression levels of EEF1 members were significantly associated with the infiltration of various immune cells and the expression of key molecules in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Conclusion EEF1D,EEF1A1,and EEF1A2 are associated with the progression of LUAD,serving as the candidate prognostic markers for LUAD.

Global profiling of lysine succinylation in human lungs.

The lysine succinylation (Ksucc) is involved in many core energy metabolism pathways and affects the metabolic process in mitochondria, making this modification highly valuable for studying diseases related to mitochondrial disorders. In this paper, we used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform the first global profiling of succinylation in human lungs under normal physiological conditions. Using an MS-based platform, we identified 1485 Ksucc sites in 568 proteins. We then compared these sites with those previously identified in human succinylome studies to investigate specific succinylated proteins and identify their possible functions in the lung and to explore the substrate preferences of succinylation modifiers in different cell lines and at different subcellular localizations. Our work expands the succinylation database and supplementary materials on the human succinylome and will thus help in further study of the function of Ksucc and regulation under related physiological and pathological conditions.

Phosphoproteome profiling of mouse liver during normal aging.

BACKGROUND: Aging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discover potential intervention methods. Old mice are frequently obese with a fatty liver. METHODS: We applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of the liver in mice aged 2 or 18 months. MaxQuant was used for quantitative analysis and PCA was used for unsupervised clustering. RESULTS: Through phosphoproteome analysis, a total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. PCA analysis of both the phosphoproteome and transcriptome data could distinguish young and old mice. However, from kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis done with phosphoproteome data, we observed high phosphorylation of fatty acid biosynthesis, ß-oxidation, and potential secretory processes, together with low phosphorylation of the Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to the aging-associated fatty liver phenotype than the differentially expressed transcripts. The phosphoproteome may reveal distinctive biological functions that are lost in the transcriptome. CONCLUSIONS: In summary, we constructed a phosphorylation-associated network in the mouse liver during normal aging, which may help to discover novel antiaging strategies.

Comprehensive Analysis of Individual Variation in the Urinary Proteome Revealed Significant Gender Differences.

Disease biomarkers are the measurable changes associated with a pathophysiological process. Without homeostatic control, urine accumulates systematic changes in the body. Thus, urine is an attractive biological material for the discovery of disease biomarkers. One of the major bottlenecks in urinary biomarker discovery is that the concentration and composition of urinary proteins are influenced by many physiological factors. To elucidate the individual variation and related factors influencing the urinary proteome, we comprehensively analyzed the urine samples from healthy adult donors (aged 20-69 years). Co-expression network analysis revealed protein clusters representing the metabolic status, gender-related differences and age-related differences in urinary proteins. In particular, we demonstrated that gender is a crucial factor contributing to individual variation. Proteins that were increased in the male urine samples include prostate-secreted proteins and TIMP1, a protein whose abundance alters under various cancers and renal diseases; however, the proteins that were increased in the female urine samples have known functions in the immune system. Nine gender-related proteins were validated on 85 independent samples by multiple reaction monitoring. Five of these proteins were further used to build a model that could accurately distinguish male and female urine samples with an area under curve value of 0.94. Based on the above results, we strongly suggest that future biomarker investigations should consider gender as a crucial factor in experimental design and data analysis. Finally, reference intervals of each urinary protein were estimated, providing a baseline for the discovery of abnormalities.

Resistin-like molecule beta augments phenotypic modulation of human aortic smooth muscle cell triggered by high glucose.

Vascular muscle cells (VSMCs) participate in the pathophysiology of atherosclerosis. Resistin-like molecule beta (Relmß) contributes to atherosclerosis development by activating macrophage. This study aims to investigate whether Relmß regulates VSMC phenotypic modulation under high glucose environment. Human aortic vascular smooth muscle cells were cultured and treated with Relmß in the presence or absence of high glucose. VSMC phenotypic modulation was assessed by expression of related markers. The migration of VSMCs was detected by wound healing assay and transwell assay. The proliferation of VSMCs was measured using CCK-8 assay. In this study, we observed that Relmß modulated VSMC phenotypic modulation by down-regulating expression of smooth muscle α-actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), and calponin while up-regulating expression of osteopontin (OPN). Relmß increased the expression of inflammatory genes in VSMCs. Relmß also augmented VSMCs migration as well as proliferation. It is worth noting that all the effects of VSMCs were enhanced upon high glucose stimulation. The phosphorylation levels of p38MAPK and ERK1/2 were increased by co-treatment with Relmß and high glucose. The p38 MAPK pathway inhibitor RWJ64809 and pERK1/2 inhibitor PD98059 significantly inhibited the proliferation of VSMCs induced by Relmß and high glucose. Our results provide evidence that Relmß augments phenotypic modulation and migration of human aortic smooth muscle cell induced by high glucose. Relmß might be a potential target for treatment of atherosclerosis induced by hyperglycemia.

A multi-level hypoglycemia early alarm system based on sequence pattern mining.

BACKGROUND: Early alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations. METHODS: Through symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system. RESULTS: The model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively. CONCLUSIONS: The proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.

[Untargeted Metabolomic Profiling of Liver and Serum in Mouse during Normal Aging].

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.

[Proteome and Acetylome Profiling of Livers in C57BL/6J Male Mice during Normal Aging].

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.

Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study.

BACKGROUND: Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima-media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population. METHODS: We performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA. RESULTS: Serum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (-, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62-12.25) and 6.93 ng/mL (4.23-9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64-0.80, P = 0.0065). Spearman's rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P < 0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors for carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein (OR = 1.085, P = 0.022). CONCLUSIONS: Circulating HSP27, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.

Pituitary Dysfunction in Patients with Intracranial Germ Cell Tumors Treated with Radiotherapy.

OBJECTIVE: To evaluate the endocrine abnormalities in intracranial germ cell tumors (iGCTs) treated with radio-therapy (RT), and to discuss the effects of RT on pituitary functions. METHODS: Seventy-seven patients diagnosed with iGCTs who had received RT and endocrine follow-up in Huashan Hospital between January 2010 and July 2017 were retrospectively analyzed, consisting of 49 germinomas and 28 NGGCTs. The median follow-up period was 50.0 months. Fifty-one patients had radiologically proved suprasellar/sellar lesions. RESULTS: The male to female ratio was 62/15. The median endocrine follow-up period was 19 (4, 42) months. The median age at the last endocrine visit was 18 (16, 20) years old. The 5-year overall and recurrence-free survival were both 98.7%. The overall prevalence of central adrenal insufficiency (CAI), central hypothyroidism (CHT), central hypogonadism (CHG), hyperprolactinemia, and central diabetes insipidus (CDI) was 57.3%, 56%, 56.6%, 35.3%, and 52.1%, respectively, after RT. Patients having suprasellar/sellar lesions showed significantly higher post-therapeutic prevalence of hypopituitarism than those who didn't. Compared to that before RT, CAI, CHT, and CHG weren't significantly improved while the levels of prolactin and the prevalence of CDI declined significantly (P =.03 and.001). The radiation doses to pituitary and hypothalamus between those with and without CAI, CHT, and CHG weren't significantly different. CONCLUSION: The prevalence of hypopituitarism was high in iGCTs, especially in those with suprasellar/sellar involvement. The levels of prolactin and the prevalence of CDI declined significantly after RT. The hypopituitarism in iGCTs was mainly induced by tumor effects, and RT showed no additional damage to pituitary functions in our study. ABBREVIATIONS: AFP = alpha-fetoprotein; CAI = central adrenal insufficiency; CDI = central diabetes insipidus; CHG = central hypogonadism; CHT = central hypothyroidism; CT = computed tomography; DA = dopamine; GH = growth hormone; ßHCG = beta-human chorionic gonadotropin; HPA = hypothalamus-pituitary-adrenal; HPG = hypothalamus-pituitary-gonadal; HPL = hyperprolactinemia; HPT = hypothalamus-pituitary-thyroid; iGCT = intracranial germ cell tumor; IGF-1 = insulin-like growth factor 1; NGGCT = nongerminomatous germ cell tumors; OS = overall survival; PFS = progression-free survival; PRL = hypothalamus-pituitary-prolactin; RT = radiotherapy.

Elevated circulating cathepsin S levels are associated with metabolic syndrome in overweight and obese individuals.

OBJECTIVE: Cathepsin S is highly expressed in subcutaneous and visceral adipose tissue. Cathepsin S correlates with central obesity and contributes to the formation and progression of atherosclerosis. Here, we sought to evaluate the association of serum cathepsin S with metabolic syndrome (MS) in overweight and obese Chinese adults. METHODS: We evaluated serum cathepsin S levels in a cross-sectional sample of 781 overweight and obese Chinese adults by ELISA. Glucose, insulin, lipid profile, inflammatory markers, and adipokines were also measured. RESULTS: Cathepsin S was significantly associated with BMI, waist circumference, waist-to-hip ratio, fasting glucose, fasting insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), systolic blood pressure, C-reactive protein (CRP), triglycerides, and HDL cholesterol (all P < 0.05). Plasma cathepsin S levels increased significantly (P = 0.045 for trend) with increasing numbers of MS components after adjustment for potential confounders. In the highest cathepsin S quartile, the MS risk was significantly higher (odds ratio 2.30; 95% confidence interval, 1.89-2.78) than in the lowest quartile after adjustment for age, gender, alcohol consumption, smoking, education, physical activity, self-reported CVD, and family history of diabetes. This association remained strong (odds ratio 1.97; 95% confidence interval, 1.72-2.48) after controlling further for CRP, adiponectin, HOMA-IR, and BMI. CONCLUSIONS: Elevated circulating cathepsin S concentrations are strongly and independently associated with MS in overweight and obese Chinese adults. Prospective studies are needed to establish the role of cathepsin S in the development of MS.

Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.

The aim of this study was to systematically evaluate the efficacy and safety of anti-interleukin-1 therapy for type 2 diabetes. A literature search of PubMed and Embase for available trials on anti-interleukin-1 therapy in type 2 diabetes was performed. The baseline characteristics, changes in HbA1c and other metabolic parameters, and adverse events were extracted from included randomized controlled trials (RCTs) and were analysed with Review Manager. Mean differences (MDs) and 95% confidence intervals (Cis) were calculated to measure differences in metabolic parameters. Odds ratio and 95% CIs were calculated for adverse event rates. Five RCTs were included in the current meta-analysis with 357 subjects undergoing anti-interleukin-1 therapy (IL-1 receptor antagonist or anti-IL-1beta antibody) and 221 controls who received placebo. The HbA1c decrement (%) of anti-interleukin-1 group was significantly higher than that of the placebo group (MD = 0.23; 95% CI, -0.39 to -0.07; P = .005). AUC of C-peptide was improved also (MD = 14.55; 95% CI, 1.81-27.28; P = .03) after anti-interleukin-1 intervention. There was no difference in the rate of adverse events (odds ratio,1.16; 95% CI, 0.90-1.49; P = .25) between 2 groups. Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.