Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

Monocyte chemoattractant protein-1 (MCP-1): an overview.

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Upstream ORFs (uORFs) are mRNA elements defined by a start codon in the 5′ UTR that is out-of-frame with the main coding sequence. Although uORFs are present in approximately half of human and mouse transcripts, no study has investigated their global impact on protein expression. Here, we report that uORFs correlate with significantly reduced protein expression of the downstream ORF, based on analysis of 11,649 matched mRNA and protein measurements from 4 published mammalian studies. Using reporter constructs to test 25 selected uORFs, we estimate that uORFs typically reduce protein expression by 30–80%, with a modest impact on mRNA levels. We additionally identify polymorphisms that alter uORF presence in 509 human genes. Finally, we report that 5 uORF-altering mutations, detected within genes previously linked to human diseases, dramatically silence expression of the downstream protein. Together, our results suggest that uORFs influence the protein expression of thousands of mammalian genes and that variation in these elements can influence human phenotype and disease.

/pdf/upstream-open-reading-frames-cause-widespread-reduction-of-1epf47a46z.pdf

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

It is expected that the projected increased usage of implantable devices in medicine will result in a natural rise in the number of infections related to these cases. Some patients are unable to autonomously prevent formation of biofilm on implant surfaces. Suppression of the local peri-implant immune response is an important contributory factor. Substantial avascular scar tissue encountered during revision joint replacement surgery places these cases at an especially high risk of periprosthetic joint infection. A critical pathogenic event in the process of biofilm formation is bacterial adhesion. Prevention of biomaterial-associated infections should be concurrently focused on at least two targets: inhibition of biofilm formation and minimizing local immune response suppression. Current knowledge of antimicrobial surface treatments suitable for prevention of prosthetic joint infection is reviewed. Several surface treatment modalities have been proposed. Minimizing bacterial adhesion, biofilm formation inhibition, and bactericidal approaches are discussed. The ultimate anti-infective surface should be “smart” and responsive to even the lowest bacterial load. While research in this field is promising, there appears to be a great discrepancy between proposed and clinically implemented strategies, and there is urgent need for translational science focusing on this topic.

https://www.mdpi.com/1422-0067/15/8/13849/pdf

Antibacterial Surface Treatment for Orthopaedic Implants

https://pure.rug.nl/ws/files/66477432/1_s2.0_S156816371830093X_main.pdf

Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases

Recent study in a group of German patients with SSc has implicated the SNP in the MCP-1 gene (−2518 A to G) as a factor of susceptibility to SSc Reflecting the need for replication of genetic association studies, we investigated if this SNP is associated with SSc in another Caucasian population MCP-1 −2518 A/G genotypes were determined using PCR-SSP in 46 SSc patients and in 449 healthy subjects, all unrelated and of Slovak (Slavonic) origin The distribution of MCP-1 −2518 A/G genotypes complied with the Hardy-Weinberg equilibrium both in patient and healthy control groups There was no difference in MCP-1 −2518*G allele frequency between SSc patients and healthy subjects (patients: 023; controls: 024; P > 05) Furthermore, MCP-1 −2518 GG homozygotes were similarly represented among SSc patients and healthy subjects (P > 05) The association of MCP-1 −2518 A/G SNP with SSc observed originally in German population was not replicated in the Slovak population

/pdf/mcp-1-2518-a-g-single-nucleotide-polymorphism-in-slovak-q2pkt4ck4v.pdf

MCP-1 -2518 A/G single nucleotide polymorphism in Slovak patients with systemic sclerosis.

Background 
Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs).


Methods 
RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls.


Results 
Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p≤0.02) and HuR (p≤0.03) proteins than control healthy PBTLs.


Conclusion 
mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis patients compared to healthy individuals. Its significance, e.g. for stability of mRNAs encoding pro-inflammatory factors, should be further explored in sarcoidosis.

/pdf/expression-profile-of-six-rna-binding-proteins-in-pulmonary-1g7wwd6oxz.pdf

Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis.

The role of the vitamin D in calcium homeostasis and bone metabolism is well known. In recent years it has been recognized that in addition to the traditional functions, vitamin D modulates a variety of processes such as host defense, inflammation and immunity. Epidemiological data indicate that low levels of vitamin D in serum are associated with impaired lung function and increased incidence of inflammatory diseases, infectious diseases and cancer. The authors studied the correlation among vitamin D levels, allergic inflammation, lung function and control of asthma and found a significant decrease of FeNO values (p= 0.0018) in children with vitamin D levels>30 ng/ml. These findings confirm that vitamin D plays a major role in bronchial inflammation.

Vitamin d and bronchial inflammation in asthmatic children.

Background: MicroRNAs (miRNAs) are implicated in pathogenesis of pulmonary sarcoidosis, namely in posttranscriptional regulation of (pro)inflammatory cytokines. Circulatory miRNAs are stable miRNAs packaged in exosomes during cellular communication that protect miRNA molecules from degradation. There has been no information on the presence of exosomal miRNA in sarcoid lung. We have, therefore, investigated 11candidate miRNAs in exosomes from sarcoid bronchoalveolar (BAL) space. Method: Exosomes were isolated from BAL fluid (BALF) from sarcoidosis patients (n=39) by differential centrifugation (3000g followed by 10000g) for 30 min each at 4°C. The supernatant was 0.2 µm filtered and centrifuged at 140000g (2 hrs at 4°C). From the obtained exosomal pellet, miRNAs was isolated and quantified using RT-qPCR. The expression data was normalized to spike-in control and BALF input volume. Result: In BALF exosomes, miR-21, -26a and -146a expression was detected with concentration (ng/µl)/ sample volume (ml) ratio ranging from 0.004-0.116 (Ct=16.4-27.3) for miR-21; 0.002-0.225 (18.9-26.9) miR-26a and 0.002-0.185 (17.9-25.0) miR-146a. Sub-analysis comparing non-smokers in radiological stage I (n=6) with stage II (n=17) showed no difference in their expression (pg0.05). MiR-15a, -129, -133a, -133b, -134, -195, -452 and -589 were not detectable in BALF exosomes. Conclusions: The implemented methodology for detection of miRNA in exosomes from BALF enabled to detect exosomal miR-21, -26a and -146a in sarcoidosis. Future analyses will focus on detailed characterization of exosomal expression profile in sarcoidosis, also in comparison with healthy subjects / diffuse lung disease. Grant support: CZ.1.07/2.3.00/30.0041, CZ.1.05./2.1.00/01.0030.

Detection of exosomal miRNA in pulmonary sarcoidosis

Background and aims. Osteoprotegerin (OPG; official gene symbol: TNFRSF11B) is considered a negative regulator of bone resorption via inhibition of osteoclast differentiation. Further, OPG expression has been detected in Prosthetic Joint Infection (PJI) a serious complication limiting the overall outcome of total joint arthroplasty (TJA). As OPG may be a candidate molecule for PJI pathogenesis, we investigated whether genetic variation in the OPG promoter, namely the SNP at position -163 was associated with PJI. Methods. OPG -163 T/C SNP (rs3102735) was genotyped by polymerase chain reaction with sequence specific primers (PCR-SSP) in 98 Czech patients with PJI and two Czech control groups: 1) aseptic TJA control [251 patients with TJA who did not develop PJI at least 6 yrs. after the surgery] and 2) population control (185 healthy control subjects without TJA). Results. The distribution of OPG -163 SNP genotypes complied with the Hardy-Weinberg equilibrium in all three groups. The allele frequencies of OPG -163 SNP were similar in patients with PJI (minor allele frequency: 0.14), those with aseptic TJA (0.13) and population controls (0.14, P>0.05). Further, there was no significant difference in genotype or phenotype frequency (carriage rate) between patients with PJI and both control groups (P>0.05). Conclusions. In a Czech population, the OPG -163 T/C SNP has not been found to be associated with PJI.

/pdf/osteoprotegerin-gene-polymorphism-is-not-associated-with-58re13igbc.pdf

Zdenka Navratilova

Papers

MCP-1 -2518 A/G single nucleotide polymorphism in Slovak patients with systemic sclerosis.

Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis.

Vitamin d and bronchial inflammation in asthmatic children.

Detection of exosomal miRNA in pulmonary sarcoidosis

Osteoprotegerin gene polymorphism is not associated with prosthetic joint infection after total joint arthroplasty in the Czech population