Polymorphisms of COTL1 gene identified by proteomic approach and their association with autoimmune disorders

To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.     

Amidase and peptidase activities of polyclonal immunoglobulin G present in the sera of patients with rheumatoid arthritis

Polyclonal Immunoglobulin (Ig) G from patients with rheumatoid arthritis (RA) and healthy subjects hydrolyzed carbobenzoxy−Val−Gly−Arg p-nitroanilide and D−Pro−Phe−Arg p-nitroanilide. RA IgG exhibited higher activity against the former substrate, but not the latter. On the other hand, RA IgG showed reduced activity against D−Pro−Phe−Arg methylcoumarinamide, when compared with those of the healthy controls. These results suggest that RA IgGs differ from normal IgGs in the substrate specificity of amidase activity. Preliminary studies have shown that two out of three RA IgG samples cleaved a pentapeptide—Gln−Arg−Arg−Arg−Ala−Ala— which is assumed to be associated with the risk of developing RA (Gregersen, P. K. et al. (1987), Arthritis Rheum. 30, 1205–1213). By contrast, virtually no cleavage of the same peptide was observed with IgG from healthy controls. A peptide analog, Gln−Arg−Arg−Trp−Ala, was not cleaved at all by any IgGs examined either from RA patients or healthy controls.     

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case–control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06–6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.     

Sequence-based analysis of 5′UTR and coding regions of CASP3 in terms of miRSNPs and SNPs in targetting miRNAs

Apoptosis is described as a mechanism of cell death occurring after adequate cellular harm. Deregulation of apoptosis occurs in many human conditions such as autoimmune disorders, ischemic damage, neurodegenerative diseases and different cancer types. Information relating miRNAs to cancer is increasing. miRNAs can affect development of cancer via many different pathways, including apoptosis. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Although polymorphisms in miRNA genes are very uncommon, SNPs in miRNA-binding sites of target genes are quite common. Many researches have revealed that SNPs in miRNA target sites improve or decrease the efficacy of the interaction between miRNAs and their target genes. Our aim was to specify miRSNPs on CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 5′UTR and coding exons of CASP3, and evaluate the effect of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. We detected 141 different miRNA binding sites (126 different miRNAs) and 7 different SNPs in binding sites of miRNA in 5′UTR and CDS of CASP3 gene. Intriguingly, miR-339-3p’s binding site on CASP3 has a SNP (rs35372903, G/A) on CASP3 5′UTR and its genomic sequence has a SNP (rs565188493, G/A) at the same nucleotide with rs35372903. Also, miR-339-3p has two other SNPs (rs373011663, C/T rs72631820, A/G) of which the first is positioned at the binding site. Here, miRSNP (rs35372903) at CASP3 5′UTR and SNP (rs565188493) at miR-339-3p genomic sequence cross-matches at the same site of binding region. Besides, miR-339-3p targets many apoptosis related genes (ZNF346, TAOK2, PIM2, HIP1, BBC3, TNFRSF25, CLCF1, IHPK2, NOL3) although it had no apoptosis related interaction proven before. This means that miR-339-3p may also have a critical effect on apoptosis via different pathways other than caspase-3. Hence, we can deduce that this is the first study demonstrating a powerful association between miR-339-3p and apoptosis upon computational analysis.     

Association of LIM Domain 7 Gene Polymorphisms and Plasma Levels of LIM Domain 7 with Dilated Cardiomyopathy in a Chinese Population

The aim of our study was to investigate the potential association of mRNA expression and plasma levels of the LIM domain 7 (LMO7) gene with the pathogenesis of dilated cardiomyopathy (DCM). Two SNPs of the LMO7 gene were genotyped in 310 patients with DCM and 415 controls. Our results showed that SNP rs7986131 (p = 0.002, OR = 1.38, 95% CI = 1.12–1.71), but not SNP rs4884021, was associated with DCM in the Han Chinese population. Haplotype analysis showed that the haplotype GT was associated with increased DCM susceptibility while AC was a protective haplotype. The Cox multivariate survival analysis indicated that the rs7986131 TT genotype (HR 1.659, 95% CI = 1.122–2.454, p = 0.011) was an independent multivariate predictor for shorter overall survival in patients with DCM. LMO7 mRNA expression and plasma LMO7 levels were significantly decreased in DCM (p < 0.0001). Spearman correlation test revealed that the plasma LMO7 level was negatively associated with left ventricular end-diastolic diameter (r = ?0.384, p = 0.01), left ventricular end-diastolic volume (r = ?0.375, p = 0.012), and brain natriuretic peptide (r = ?0.482, p = 0.001). Our study suggested that the LMO7 gene may play an important role in the pathogenesis of DCM in the Han Chinese population.     

Relationship between the level of essential metal elements in human hair and coronary heart disease

Studies on epidemics have demonstrated the relationship between coronary heart disease (CHD) and mineral substances, such as selenium, calcium, magnesium, sodium, potassium, copper, zinc, iron, manganese, and vanadium, in human bodies. In this study, instrumental neutron activation analysis (INAA) and flame atomic absorption spectrophotometry (FAAS) were applied to evaluate the levels of selenium, calcium, magnesium, sodium, potassium, copper, zinc, and iron in healthy individuals and CHD patients. Hair samples were collected from 42 healthy participants and 28 diagnosed CHD patients. Calcium, magnesium, copper, and zinc levels in healthy individuals are significantly higher than the levels found in the patients (p < 0.01). Calcium/selenium ratio is also significantly higher in healthy individuals (p < 0.05). Based on the possible synergies and/or antagonisms of elements and their absorption and metabolism, magnesium/calcium, zinc/copper, and sodium/potassium ratios showed positive relevance (p < 0.01).     

Prognostic role of genetic biomarkers in clinical progression of prostate cancer

The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT–GT), rs486907 (AG) and rs3747531 (CG–CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.     

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN. We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to several clinical and pathological parameters. Genotyping data showed significant differences between IgAN patients and controls in the frequency of rs2039620, rs12034829, and rs3795443. On comparison of patients with proteinuria to those without proteinuria (≤ or > 4 mg/m²/h), rs12043633 was significantly different between the two groups. With regard to maximum proteinuria (≤ or > 4 mg/m²/h), rs3795443, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. For patients with and without gross hematuria, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. The rs3795443 was found to be associated with progression of pathological findings. Our results suggest that ENAH polymorphisms are associated with increased susceptibility, development of proteinuria and gross hematuria, and pathological progression of childhood IgAN.     

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.     

The influence of MTHFR C677T polymorphism in chronic lymphocytic leukemia

Some factors have been associated with the etiology of chronic lymphocytic leukemia (CLL), among them the Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. The aim of this study was to evaluate the role of MTHFR C677T polymorphism in CLL. A case‐control study was conducted with 219 individuals from Brazilian central population. MTHFR C677T polymorphism was determined through PCR‐RFLP followed by PAGE. The T allele frequence was higher in patients diagnosed with CLL than healthy subjects. However, when stratified by gender, the TT genotype was exclusively found in men diagnosed with CLL (p < 0.05). Adjusted multiple logistic regression analysis demonstrated that age was significantly linked to CLL predisposition (odds ratio = 1.08; p < 0.001). Studies evaluating the influence of genetic factors may provide insights on susceptibility for CLL.     

A meta-analysis of tumor necrosis factor (TNF) gene polymorphism and susceptibility to influenza A (H1N1)

PurposeThe aim of the study was to comprehensively evaluate the associations between tumor necrosis factor (TNF) gene polymorphism and influenza A (H1N1) susceptibility.MethodsThe relevant studies were identified through a search of PubMed, Embase, and Cochrane library database until February 29, 2020, without language restrictions. Two independent reviewers extracted the data, and any discrepancies were resolved by consensus. The quality of the eligible article was evaluated by Newcastle-Ottawa Quality Assessment Scale (NOS). Egger’s test was applied to evaluate publication bias. All these analyses were performed using Stata15.1 software.ResultsA total of 5 studies with 474 cases and 805 controls were included. The results of meta-analysis showed that there were statistically significant for rs361525 in allelic model (A vs. G) [OR = 2.46 (1.10, 5.52)] and for rs1800750 in dominant model (AA + GA vs. GG) [OR = 2.42 (1.24, 4.71)] in cases vs. controls. Furthermore, subgroup analysis for race showed that for rs361525 in allelic model (A vs. G), there were significant differences for Caucasian [OR = 3.64 (1.18, 11.23)] and no significant difference for Mexican [OR = 2.25 (0.82, 6.13)] in cases vs. controls. There was publication bias for rs361525 in dominant model (AA + GA vs. GG, p = 0.042) and rs1800629 in recessive model (AA vs. GG + GA, p < 0.001).ConclusionsCaucasian with A site mutation of -238TNF G/A (rs361525) was more susceptible to influenza A (H1N1).The -376 dominant model AA + GA of TNF genes was associated with the susceptibility to influenza A (H1N1). However, more studies with large sample size are needed to confirm the results.     

Analysis of the variations in IL-28RA gene and their association with allergic rhinitis

IL-28RA is one of the important candidate genes for complex trait of genetic diseases, but there is no published information of the genetic variation in this gene. We scanned the seven exons and their boundary introns sequence of IL-28RA including the promoter regions to analyze genetic variation sites, and identified eighteen single nucleotide polymorphisms (SNPs) and two variation sites. We chose seven SNPs (g.-1193 A>C, g.-30 C>T, g.17654 C>T, g.27798 A>G, g.31265 C>T, g.31911 C>T and g.32349 G>A) of them for large sample size genotyping, and assessed the association of genotype and allele frequencies of these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. We also compared the genotype frequencies between Korean controls and Han Chinese control or Korean Chinese control. We investigated the frequencies of haplotype constructed by these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. Our results suggested that the g.32349 G>A polymorphism of IL-28RA might be associated with susceptibility to allergic rhinitis (P=0.032), but seems to have no relationship with serum total IgE levels. The haplotype frequencies by these SNPs also show significant association between controls and allergic rhinitis patients.     

Determination of trace elements in blood samples of patients affected by multiple sclerosis from Iran by neutron activation analysis

Multiple sclerosis (MS) is a neurological autoimmune disease in which the immune system attacks the central nervous system for unknown reasons and causes several damages to human body by demyelinating the nerve cells. One of the possible cause of this disease is the abnormality levels of some trace elements such as Br, Fe, Rb, Sb, As, and Zn in human body. This study attempts to measure the levels of four trace elements of Br, Fe, Rb, and Zn in the patients?? blood samples and compare them with control samples from healthy individuals. It should be noted that the objectives set out partly met. According to the obtained results, the differences between the levels of Br, Fe, and Rb in patients?? blood samples and control was not significant (P?>?0.05). However, the average level of Zn between samples and controls showed a significant difference (P?<?0.05). Therefore the lower level of Zn in blood is likely to be a major cause of MS emergence. Furthermore, by using the concentration level of Zn as indicator, it was revealed that the risk of MS infection rises as the number of pregnancies increase.     

Vitamin E Can Ameliorate Oxidative Damage of Ovine Hepatocytes In Vitro by Regulating Genes Expression Associated with Apoptosis and Pyroptosis,but Not Ferroptosis

(1) Background: the current research was conducted to investigate the potential non-antioxidant roles of vitamin E in the protection of hepatocysts from oxidative damage. (2) Methods: primary sheep hepatocytes were cultured and exposed to 200, 400, 600, or 800 μmol/L hydrogen peroxide, while their viability was assessed using a CCK-8 kit. Then, cells were treated with 400 μmol/L hydrogen peroxide following a pretreatment with 50, 100, 200, 400, and 800 μmol/L vitamin E and their intracellular ROS levels were determined by means of the DCF-DA assay. RNA-seq, verified by qRT-PCR, was conducted thereafter: non-treated control (C1); cells treated with 400 μmol/L hydrogen peroxide (C2); and C2 plus a pretreatment with 100 μmol/L vitamin E (T1). (3) Results: the 200–800 μmol/L hydrogen peroxide caused significant cell death, while 50, 100, and 200 μmol/L vitamin E pretreatment significantly improved the survival rate of hepatocytes. ROS content in the cells pretreated with vitamin E was significantly lower than that in the control group and hydrogen-peroxide-treated group, especially in those pretreated with 100 μmol/L vitamin E. The differentially expressed genes (DEGs) concerning cell death involved in apoptosis (RIPK1, TLR7, CASP8, and CASP8AP2), pyroptosis (NLRP3, IL-1β, and IRAK2), and ferroptosis (TFRC and PTGS2). The abundances of IL-1β, IRAK2, NLRP3, CASP8, CASP8AP2, RIPK1, and TLR7 were significantly increased in the C1 group and decreased in T1 group, while TFRC and PTGS2 were increased in T1 group. (4) Conclusions: oxidative stress induced by hydrogen peroxide caused cellular damage and death in sheep hepatocytes. Pretreatment with vitamin E effectively reduced intracellular ROS levels and protected the hepatocytes from cell death by regulating gene expression associated with apoptosis (RIPK1, TLR7, CASP8, and CASP8AP2) and pyroptosis (NLRP3, IL-1β, and IRAK2), but not ferroptosis (TFRC and PTGS2).     

Blood-copper and zinc levels and consequences of cardiovascular complications: a study by INAA and FAAS

To understand the role of Cu and Zn in human blood both in controls as well as in cardiovascular (CVD) patients, whole blood samples of 181 CVD and 185 controls between the ages of 20–66 years were investigated. Instrumental neutron activation analysis (INAA) and flame atomic absorption spectrophotometric techniques were successfully employed to quantification Cu and Zn levels. The mean blood-Cu levels (1.50 mg L⁻¹) were found as enhanced whereas Zn levels (5.88 mg L ⁻¹) were reduced in cardiovascular patients group as compared to 0.90 and 6.70 mg L⁻¹ for Cu and Zn respectively in controls. Cu/Zn ratios for CVD patients are also higher than in control subjects. Negative correlation exists between Cu and Zn levels in both controls and patient groups. However, when the CVD patients were checked for their systolic and diastolic pressure it was found that copper concentrations in these patients was significantly increased (p < 0.001) with the rise of blood systolic pressure so a positive correlation was observed between copper and systolic pressure. Zn on the other hand has an inverse relation with systolic as well as diastolic pressure (p < 0.001). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglyceride (TG) in blood samples have also been determined and their probable role in the CVD complication has been observed. A positive correlation of blood-Cu with TC, TG, and LDL-C indicates that rise in blood-Cu levels may initiate the development of CVD. An increase in Cu/Zn ratio can instigate the cardiovascular risk factor. The findings from this study can definitely update our knowledge of the role of Cu and Zn in the development of CVD risk in humans.     

Analysis of trace elements in blood sera of breast cancer patients by particle induced X-ray emission

Trace elemental imbalance in human beings is postulated to exert action, directly or indirectly, on the carcinogenic process. The objective of this study was to evaluate the levels of trace elements in blood sera of breast cancer patients and analyze their alteration with respect to healthy controls. This work was also intended to establish the role played by the trace elements in carcinogenic process. Particle induced X-ray emission (PIXE) technique was used for trace elemental analysis of blood sera of breast cancer patients and healthy controls. The PIXE measurements were carried out using a 2.5?MeV collimated proton beam from the 3 MV Tandem Pelletron accelerator at Institute of Physics, Bhubaneswar, India. On comparing the trace elemental content in the sera of breast cancer patients with those of control subjects, significant variations were observed in the levels of most of the trace elements. The serum levels of almost all the elements except Fe and Cu were observed to be depressed in cancer patients with respect to normal subjects. However, this variation was significant only for Ti (P?<?0.00005), Cr (P?<?0.005), Mn (P?<?0.0005), Ni (P?<?0.01), Zn (P?<?0.000001), and Se (P?<?0.05). On the other hand, significant elevations were observed in serum Fe (P?<?0.05) and Cu (P?<?0.005) levels in cancer patients. The findings presented in this paper give guidelines for future study into the possible roles and interactions of essential trace elements in the breast carcinogenic process.     

Genome-wide association studies combined with k-fold cross-validation identify rs17822931 as an ancestry-informative marker in Han Chinese population

DNA-based ancestry inference has long been a research hot spot in forensic science. The differentiation of Han Chinese population, such as the northern-to-southern substructure, would benefit forensic practice. In the present study, we enrolled participants from northern and southern China, each participant was genotyped at ∼400 K single-nucleotide polymorphisms (SNPs) and data of CHB and CHS from 1000 Genomes Project were used to perform genome-wide association analyses. Meanwhile, a new method combining genome-wide association study (GWAS) analyses with k-fold cross-validation in a small sample size was introduced. As a result, one SNP rs17822931 emerged with a p-value of 7.51E − 6. We also simulated a huge dataset to verify whether k-fold cross-validation could reduce the false-negative rate of GWAS. The identified ABCC11 rs17822931 has been reported to have allele frequencies varied with the geographical gradient distribution in humans. We also found a great difference in the allele frequency distributions of rs17822931 among five different cohorts of the Chinese population. In conclusion, our study demonstrated that even small-scale GWAS can also have potential to identify effective loci with implemented k-fold cross-validation method and shed light on the potential maker of rs17822931 in differentiating the north-to-south substructure of the Han Chinese population.     

Thermal stability and sensitivity of RDX-based aluminized explosives

The thermal decomposition characteristics and thermal sensitivity are key indicators for reflecting the thermal stability of explosives in storage and application. The thermal decompositions in different degrees are used to determine the dominant factor which controls the thermal stability of composite explosive. Four kinds of RDX-based aluminized explosives are marked as RA1, RA2, RA3, and RA4 with the Al content increasing from 10 to 40 mass%. The initial thermal decomposition behaviors were studied by DPTA and the complete thermal decompositions were studied by DSC and TG. The thermal sensitivities were characterized by 5-s explosion point. The effects of micron-sized Al particles and their contents on thermal decomposition were investigated. The evolved gas amount (V _i) from DPTA test follows RA3 < RA4 < RA2 < RA1, indicating that RA3 has the best thermal stability at ambient storage conditions. However, according to TG and DSC tests, the characteristic temperatures of thermal decomposition (T _p, T _b, and T _SADT), the thermodynamic parameters (?H _e, ?S ^≠, and ?H ^≠), the kinetic parameters (E _a and A), and the 5-s explosion points all follow RA4 < RA3 < RA2 < RA1. The results indicate that the Al particles play different roles in the different degrees of thermal decomposition. In the initial decomposition, the Al particles have not been activated and are considered as inert materials that hinder the decomposition of explosive. In the complete decomposition, the Al particles catalyze the thermal decomposition, and such catalysis becomes more obvious as the Al content increases to a certain degree.     

Determination of creatinine-related molecules in saliva by reversed-phase liquid chromatography with tandem mass spectrometry and the evaluation of hemodialysis in chronic kidney disease patients

The serum concentrations of creatinine (Cre) and urea are used for the determination of the renal function. However, the use of blood is not always suitable due to the invasive, hygienic and infection problems during its sample collection and handling. In contrast, saliva is relatively clean and the samples can be quickly and noninvasively collected and easily stored. Therefore, the simultaneous determination of Arginine (Arg), creatine (Cr) and Cre in the saliva of chronic kidney disease (CKD) patients was performed by UPLC-ESI-MS/MS together with the saliva of healthy volunteers. The evaluation of hemodialysis of CKD patients was also carried out by the determinations before and after the dialysis. An HS-F5 column was used for the simultaneous determination of Arg, Cr and Cre in the saliva. These molecules were rapidly separated within 4 min and sensitively determined by the multiple reaction monitoring (MRM) of the precursor ion [M+H]⁺ → product ions (m/z 175.1 → 70.1 for Arg; m/z 132.0 → 44.1 for Cr; m/z 114.0 → 44.1 for Cre). The concentration of Cre in the CKD patients was higher than that in the healthy persons. The concentrations of Cre in the saliva of the patients before hemodialysis were moderately correlated with the serum Cre concentrations (R² = 0.661). Furthermore, the concentration in the saliva obviously decreased after hemodialysis (before 0.73 mg/dL, after 0.25 mg/dL; p < 0.02). Thus, the proposed detection method using saliva by UPLC-MS/MS is useful for the evaluation of the renal function in CKD patients. The present method offers a new option for monitoring the hemodialysis of CKD patients.