Calprotectin (S100A8/S100A9): a key protein between inflammation and cancer

Background

Calprotectin (S100A8/S100A9), a heterodimeric EF-hand Ca²⁺?binding protein, are abundant in cytosol of neutrophils and are involved in inflammatory processes and several cancerous pathogens.

Objective

The purpose of the present systematic review is to evaluate the pro- and anti-tumorigenic functions of calprotectin and its relation to inflammation.

Materials and methods

We conducted a review of studies published in the Medline (1966–2018), Scopus (2004–2018), ClinicalTrials.gov (2008–2018) and Google Scholar (2004–2018) databases, combined with studies found in the reference lists of the included studies.

Results

Elevated levels of S100A8/S100A9 were detected in inflammation, neoplastic tumor cells and various human cancers. Recent data have explained that many cancers arise from sites of infection, chronic irritation, and inflammation. The inflammatory microenvironment which largely includes calprotectin, has an essential role on high producing of inflammatory factors and then on neoplastic process and metastasis.

Conclusion

Scientists have shown different outcomes in inflammation, malignancy and apoptosis whether the source of the aforementioned protein is extracellular or intracellular. These findings are offering new insights that anti-inflammatory therapeutic agents and anti-tumorigenic functions of calprotectin can lead to control cancer development.

     

HLA‐DRA is associated with Parkinson's disease in Iranian population

The rs3129882, a noncoding variant in HLA‐DR, was found to be associated with Parkinson's disease (PD) using several genome‐wide association studies. The aim of this replication study was to explore the relationship between this variant and PD in Iranian population. Genomic DNA was extracted from peripheral blood samples, and the rs3129882 SNP was genotyped using a PCR‐RFLP method in 520 PD patients and 520 healthy Iranian controls. Significant differences were found in allele frequencies between patients and controls (χ² = 4.64, P = 0.031). Under additive and dominant models, the association of the SNP with PD risk is significant, where the A allele was observed to be protective. The results suggest that rs3129882 polymorphism may be a risk factor for PD in Iranian. This is the first study reporting such an association in this population. More replication studies are needed to confirm this data.     

Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine

We have investigated whether poly(I:C) Toll-like receptor 3 (TLR3) and resiquimod Toll-like receptor 7 (TLR7) agonists can serve as vaccine adjuvants and promote the efficiency of therapeutic DNA vaccination against tumors expressing the human papilloma virus 16 (HPV-16) E7 protein. For this purpose, C57BL/6 mice were inoculated with 2 × 10⁵ TC-1 cells, and they were then immunized with HPV-16 E7 DNA vaccine alone or with 50 μg of resiquimod or poly(I:C) individually. We found that poly(I:C) and resiquimod could induce more antigen-specific lymphocyte proliferation and cytolytic activity compared to vaccination with E7 DNA alone. While E7 DNA had no significant inhibitory effect on tumor growth, co-administration of poly(I:C) and resiquimod with E7 DNA induced significant tumor regression. Peripheral and local cytokine assays demonstrated that co-administration of poly(I:C) and resiquimod with E7 DNA induced circulating antigen-specific IFN-γ and nonspecific intratumoral IL-12. TLR3 and TLR7 agonists can be used to enhance the immune response to DNA vaccine immunogens. Taken together, these data indicate that combined vaccination with DNA encoding HPV-16 E7 plus TLR agonists provides a strategy for improving the efficacy of a vaccine as a possible immunotherapeutic strategy for cervical cancer.     

The Production and Characterization of Novel Heavy-Chain Antibodies Against the Tandem Repeat Region of MUC1 Mucin

Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH₁). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. K_a values of specific polyclonal anti-peptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 × 10¹⁰ M^{? 1} and 1.4 × 10¹⁰ M^{? 1} respectively.     

Clinicopathological findings of a natural outbreak of Theileria annulata in cattle: an emerging disease in southern Iran

Theileriosis is an economically important hemoprotozoal disease with high morbidity and mortality in cattle. The present study reported the pathological features of a natural outbreak of tropical bovine theileriosis due to Theileria annulata in Fars Province, southern Iran. T. annulata was confirmed by the presence of T. annulata piroplasms in the blood smears and also by polymerase chain reaction test. On necropsy, pale mucous membranes and petechial and ecchymotic hemorrhages in the mucosal and serosal surfaces together with lymphadenopathy were observed. The liver was friable, yellowish, and larger than normal. Hemorrhages and punched-out ulcers were observed in the abomasal mucous membrane. Severe petechial hemorrhages were seen in the skin particularly in the hairless areas. Pulmonary edema and emphysema with petechial and ecchymotic hemorrhagic foci in the lungs were evident. The main histological changes were proliferation of lymphocytes in the lymph nodes and proliferation of macrophages, lymphocytes, and plasma cells in the spleen, Peyer's patches, portal tracts of the liver, and interstitial tissue of the kidneys. The mucous membrane of the abomasum showed numerous multifocal areas of necrosis and ulceration, and the submucosal area and lamina propria adjacent to these lesions showed hyperemia and hemorrhages, with mononuclear cell infiltration. The skin showed multifocal necrotic changes, petechial and ecchymotic hemorrhages, and chronic dermatitis. The schizonts of Theileria were evident in the cytoplasm of the lymphocytes and macrophages of the lymph nodes, spleen, and skin. Molecular examination revealed that these animals were infected with T. annulata. The present study describes the clinicopathological findings of bovine tropical theileriosis in an unpredictable weather condition.     

Multi-level basis selection of wavelet packet decomposition tree for heart sound classification

Wavelet packet transform decomposes a signal into a set of orthonormal bases (nodes) and provides opportunities to select an appropriate set of these bases for feature extraction. In this paper, multi-level basis selection (MLBS) is proposed to preserve the most informative bases of a wavelet packet decomposition tree through removing less informative bases by applying three exclusion criteria: frequency range, noise frequency, and energy threshold. MLBS achieved an accuracy of 97.56% for classifying normal heart sound, aortic stenosis, mitral regurgitation, and aortic regurgitation. MLBS is a promising basis selection to be suggested for signals with a small range of frequencies.     

Antibacterial,antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles fabricated from Mespilus germanica extract against multidrug resistance of Klebsiella pneumoniae clinical strains

The aim of the present work was to investigate the antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles (AgNPs) fabricated from Mespilus germanica extract against multidrug-resistant (MDR) Klebsiella pneumoniae strains. Fifty strains of K. pneumoniae were isolated from various clinical specimens. Biofilm-forming strains were identified using Congo red agar and polymerase chain reaction (PCR) techniques. Subsequently, the antibacterial activity of phytosynthesized AgNPs on MDR K. pneumoniae strains was investigated by broth microdilution assay and agar well-diffusion method. Finally (in the last step), the antibiofilm activity of phytosynthesized AgNPs was determined using microtiter plate assay and real-time PCR (RT-PCR) methods for the analysis of type 3 fimbriae (mrkA) and quorum-sensing system (luxS) gene expression. The results of this study showed that the phytosynthesized AgNPs had a spherical nanostructure with the mean size of 17.60 nm. The AgNPs exhibited dose-dependent antibacterial activity. The results of the microtiter plate and RT-PCR methods show that AgNPs inhibited the biofilm formation in MDR K. pneumoniae strains, and the expressions of mrkA and luxS genes were downregulated significantly in MDR strains after treatment with a subminimum inhibitory concentration of AgNPs. In conclusion, AgNPs effectively prevent the formation of biofilms and kill bacteria in established biofilms, which suggests that AgNPs might be a promising candidate for the prevention and treatment of biofilm-related infections caused by MDR K. pneumoniae strains.     

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis

Background and ObjectiveChronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients.Materials and MethodsTotal RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies.ResultsResults point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don''t find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05).ConclusionThese findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.     

Effect of eccentric and concentric contraction mode on myogenic regulatory factors expression in human vastus lateralis muscle

Skeletal muscle contractions are caused to release myokines by muscle fiber. This study investigated the myogenic regulatory factors, as MHC I, IIA, IIX, Myo-D, MRF4, Murf, Atrogin-1, Decorin, Myonection, and IL-15 mRNA expression in the response of eccentric vs concentric contraction. Eighteen healthy men were randomly divided into two eccentric and concentric groups, each of 9 persons. Isokinetic contraction protocols included maximal single-leg eccentric or concentric knee extension tasks at 60°/s with the dominant leg. Contractions consisted of a maximum of 12 sets of 10 reps, and the rest time between each set was 30 s. The baseline biopsy was performed 4 weeks before the study, and post-test biopsies were taken immediately after exercise protocols from the vastus lateralis muscle. The gene expression levels were evaluated using Real-Time PCR methods. The eccentric group showed a significantly lower RPE score than the concentric group (P?≤?0.05). A significant difference in MyoD, MRF4, Myonection, and Decorin mRNA, were observed following eccentric or concentric contractions (P?≤?0.05). The MHC I, MHC IIA, IL-15 mRNA has been changed significantly compared to the pre-exercise in the concentric group (P?≤?0.05). While only MHC IIX and Atrogin-1 mRNA changed significantly in the eccentric group (P?≤?0.05). Additionally, the results showed a significant difference in MyoD, MRF4, IL-15, and Decorin at the follow-up values between eccentric or concentric groups (P?≤?0.05). Our findings highlight the growing importance of elucidating the different responses of muscle growth factors associated with a myogenic activity such as MHC IIA, Decorin, IL-15, Myonectin, Decorin, MuRF1, and MHC IIX mRNA in following various types of exercise.