Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) Reduces Allergic Inflammation of Ovalbumin-Sensitized Mice.

Background Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug. Objectives We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model. Methods We divided 40 four-week-old BALB/c mice into four groups: control group ( n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis. Results Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group. Conclusions Aba suppresses allergic inflammation and appears to be a good treatment for AR.

Improvement of Growth Retardation and Related Immunodeficiency by Dietary Intervention with Crackers Containing Animal Source Ingredients in Malnourished Rats

Hidden hunger is a risk factor for many health problems, including stunting, which is one of the globally prevalent signs of malnutrition. Stunting can be reduced through feeding on animal source foods. In our study, some animal source foods (egg, butter, yoghurt, and white cheese) in addition to other nutritious ingredients (wheat flour, minced fresh carrot, wheat germ, yeast, and iodine salt) were used to prepare four samples of crackers, with different taste (cumin, paprika, tomato, and cheese). The dough from all ingredients was prepared, flattened, cut then baked to prepare the crackers. These crackers were organoleptically and physically evaluated. Antioxidant activity, total phenolic content (TPC) and total flavonoid contents of the crackers’ samples were determined. The cumin-flavored crackers (the highest in TPC, flavonoids, and antioxidant activity) was evaluated for its macro-and micronutrients and studied in malnourished rats. Two groups of rats (each of 12) were fed on a balanced diet and a protein-deficient diet, respectively for 3 weeks. Six rats from each group were sacrificed and the remaining rats were fed on a balanced diet and diet supplemented with the cumin-flavored crackers, respectively for 5 weeks. The cumin-flavored crackers (100 g) contained 15.64 g protein, 231.00 mg calcium, 4.00 mg zinc, 83.75 µg iodine, arginine (16.53 mg/g protein), and lysine (19.30 mg/g protein). Malnutrition, immunodeficiency (as evidenced by a drop in cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8) and CD4/CD8 ratio), and stunting (as evidenced by a decrease in rat length, femur length, and insulin growth factor-1) were all observed in rats fed a protein-deficient diet for 3 weeks. Also, femur calcium and magnesium decreased in the malnourished rats. The dietary intervention with the cumin-flavored crackers reversed the reduction in aforementioned parameters in the malnourished rats. The cumin-flavored crackers may improve growth retardation and related immunodeficiency in previously malnourished rats.

Putative Concussion Biomarkers Identified in Adolescent Male Athletes Using Targeted Plasma Proteomics

Sport concussions can be difficult to diagnose and if missed, they can expose athletes to greater injury risk and long-lasting neurological disabilities. Discovery of objective biomarkers to aid concussion diagnosis is critical to protecting athlete brain health. To this end, we performed targeted proteomics on plasma obtained from adolescent athletes suffering a sports concussion. A total of 11 concussed male athletes were enrolled at our academic Sport Medicine Concussion Clinic, as well as 24 sex-, age- and activity-matched healthy control subjects. Clinical evaluation was performed and blood was drawn within 72 h of injury. Proximity extension assays were performed for 1,472 plasma proteins; a total of six proteins were considered significantly different between cohorts (P < 0.01; five proteins decreased and one protein increased). Receiver operating characteristic curves on the six individual protein biomarkers identified had areas-under-the-curves (AUCs) for concussion diagnosis ≥0.78; antioxidant 1 copper chaperone (ATOX1; AUC 0.81, P = 0.003), secreted protein acidic and rich in cysteine (SPARC; AUC 0.81, P = 0.004), cluster of differentiation 34 (CD34; AUC 0.79, P = 0.006), polyglutamine binding protein 1 (PQBP1; AUC 0.78, P = 0.008), insulin-like growth factor-binding protein-like 1 (IGFBPL1; AUC 0.78, P = 0.008) and cytosolic 5'-nucleotidase 3A (NT5C3A; AUC 0.78, P = 0.009). Combining three of the protein biomarkers (ATOX1, SPARC and NT5C3A), produced an AUC of 0.98 for concussion diagnoses (P < 0.001; 95% CI: 0.95, 1.00). Despite a paucity of studies on these three identified proteins, the available evidence points to their roles in modulating tissue inflammation and regulating integrity of the cerebral microvasculature. Taken together, our exploratory data suggest that three or less novel proteins, which are amenable to a point-of-care immunoassay, may be future candidate biomarkers for screening adolescent sport concussion. Validation with protein assays is required in larger cohorts.

Recent Insights into Human Endometrial Peptidases in Blastocyst Implantation via Shedding of Microvesicles

Blastocyst implantation involves multiple interactions with numerous molecules expressed in endometrial epithelial cells (EECs) during the implantation window; however, there is limited information regarding the molecular mechanism underlying the crosstalk. In blastocysts, fibronectin plays a major role in the adhesion of various types of cells by binding to extracellular matrix proteins via the Arg-Gly-Asp (RGD) motif. In EECs, RGD-recognizing integrins are important bridging receptors for fibronectin, whereas the non-RGD binding of fibronectin includes interactions with dipeptidyl peptidase IV (DPPIV)/cluster of differentiation (CD) 26. Fibronectin may also bind to aminopeptidase N (APN)/CD13, and in the endometrium, these peptidases are present in plasma membranes and lysosomal membranes. Blastocyst implantation is accompanied by lysosome exocytosis, which transports various peptidases and nutrients into the endometrial cavity to facilitate blastocyst implantation. Both DPPIV and APN are released into the uterine cavity via shedding of microvesicles (MVs) from EECs. Recently, extracellular vesicles derived from endometrial cells have been proposed to act on trophectoderm cells to promote implantation. MVs are also secreted from embryonal stem cells and may play an active role in implantation. Thus, crosstalk between the blastocyst and endometrium via extracellular vesicles is a new insight into the fundamental molecular basis of blastocyst implantation.

Novel SNPs and haplotypes identified in the CD4 gene and their influence on deregressed MACE EBV indexes of milk-related traits in Simmental breed

Cluster of differentiation 4 (CD4) is the accessory protein non-covalently bound to the T cell receptor that recognizes an invariant region of MHC class II on antigen presenting cells. Its cytoplasmic tail, physically associated with a protein tyrosine kinase, is important in the activation of helper/inducer T lymphocytes. In Bos taurus, CD4 gene is located on chromosome 5 from which two isoforms are transcribed, with a different number of amino acids due to splicing of exon 7 and variation in the reading frame. The aim of this study was to investigate the sequence of the entire CD4 gene in Simmental sires to evaluate the effects of genomic variants on the indexes of the bulls for milk, fat and protein yields, as well as somatic cell score. The associations among genomic variants and indexes were analysed using the Allele and GLM procedures of SAS 9.4. The analysis indicated that only four of the thirty-one identified SNPs influenced the considered traits. Identified variants insist on coding zones and intronic sequences, where we revealed the presence of sites for transcription factors. To evaluate the existence of haplotypic effects, combinations among the four genomic variants (SNP 3, SNP 8, SNP 11 and SNP 19) were investigated. Six different haplotypic alleles were identified, but only four of them were frequent enough to allow for an evaluation of any haplotypic effect (at least six copies in the examined sample): Hap1, Hap2, Hap3 and Hap6. The analysis of associations between the selected haplotypes in the CD4 gene with milk related indexes showed that bulls with Hap2 (T-A-C-C) had better indexes for milk and protein yields (P < 0.05), whereas the presence of the Hap1 haplotype (A-G-A-T) caused a significant decrease of the index for protein yield (P < 0.05). Frequencies of the two alleles Hap1 and Hap2 (9 and 36% respectively) make them of interest for their possible inclusion in breeding schemes and support the hypothesis of considering this gene as a candidate for the improvement of milk-related traits in the Simmental breed.

Parasitic and Vector-Borne Infections in HIV-Positive Patients in Slovakia—Evidence of an Unexpectedly High Occurrence of Anaplasma phagocytophilum

In HIV (human immunodeficiency virus) infected people, the immunodeficiency caused by a reduced level of CD4 (cluster of differentiation 4) T-lymphocytes increases the risk of infectious diseases. Additionally, in individuals with immunologically compromising conditions, tick-borne or some parasitic pathogens may cause chronic, debilitating opportunistic infections and even death. The study aimed at determining the IgG seropositivity of HIV-infected patients to Toxoplasma gondii, Toxocara spp., Echinococcus multilocularis, and E. granulosus s.l. and performing the molecular identification of T. gondii and some tick-borne pathogens, namely, Borrelia spp., Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., and Bartonella spp. Out of 89 HIV-positive patients, specific IgG antibodies to T. gondii were detected in 17 (19.1%) and to Borrelia spp. in 12 (13.5%) individuals. Seropositivity to Toxocara spp., E. multilocularis, and E. granulosus s.l. was not recorded. Molecular approaches showed positivity to T. gondii in two (2.2%) patients, and 11 (12.4%) individuals had positive PCR signal for the msp2 gene of A. phagocytophilum. Relatively high prevalence of A. phagocytophilum in HIV-positive patients suggests that these people are more susceptible to some vector-borne pathogens. The presence of opportunistic infections may pose a health risk for patients with weakened immune systems, and should not be neglected during the regular monitoring of the patient’s health status.

Prognostic and Genomic Analysis of Proteasome 20S Subunit Alpha (PSMA) Family Members in Breast Cancer

The complexity of breast cancer includes many interacting biological processes, and proteasome alpha (PSMA) subunits are reported to be involved in many cancerous diseases, although the transcriptomic expression of this gene family in breast cancer still needs to be more thoroughly investigated. Consequently, we used a holistic bioinformatics approach to study the PSMA genes involved in breast cancer by integrating several well-established high-throughput databases and tools, such as cBioPortal, Oncomine, and the Kaplan–Meier plotter. Additionally, correlations of breast cancer patient survival and PSMA messenger RNA expressions were also studied. The results demonstrated that breast cancer tissues had higher expression levels of PSMA genes compared to normal breast tissues. Furthermore, PSMA2, PSMA3, PSMA4, PSMA6, and PSMA7 showed high expression levels, which were correlated with poor survival of breast cancer patients. In contrast, PSMA5 and PSMA8 had high expression levels, which were associated with good prognoses. We also found that PSMA family genes were positively correlated with the cell cycle, ubiquinone metabolism, oxidative stress, and immune response signaling, including antigen presentation by major histocompatibility class, interferon-gamma, and the cluster of differentiation signaling. Collectively, these findings suggest that PSMA genes have the potential to serve as novel biomarkers and therapeutic targets for breast cancer. Nevertheless, the bioinformatic results from the present study would be strengthened with experimental validation in the future by prospective studies on the underlying biological mechanisms of PSMA genes and breast cancer.