Effect of transplanted cells with CD184 and CD26 expressions and reconstitution of CD3+ lymphocyte population on long-term survival after autologous hematopoietic stem cell transplantation for multiple myeloma.

Autologous hematopoietic stem cell transplantation (auto-SCT) is the recommended treatment for responding patients with multiple myeloma (MM). However, we do not know the risk factors influencing long-term survival without progression after auto-SCT. Therefore, this prospective study aimed to investigate the influence of transplanted cells with cluster of differentiation (CD)184+ expression, CD26+ lymphocytes and monocytes, and reconstitution of CD3+ lymphocytes on overall survival (OS) and progression-free survival (PFS) after auto-SCT in MM. Forty-eight patients with MM underwent auto-SCT at our center from 2011 to 2013. The numbers of CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes were measured in the harvested material. In addition, the number of lymphocyte subpopulations (CD3+ lymphocytes, helpers, suppressors, natural killer (NK), cytotoxic NK, and B lymphocytes) was measured in peripheral blood during regeneration after auto-SCT. Flow cytometry was performed in both cases. The median OS was 92 months. Our analysis revealed a statistically significant effect of the number of transplanted CD184+ cells on OS and a statistically significant correlation between PFS and the number of transplanted CD184+ cells and reconstitution of CD3+ lymphocytes. In conclusion, our study showed that the increasing numbers of transplanted CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes augmented the risk of death.

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis.

BACKGROUND AND OBJECTIVES: The effect of mogamulizumab in cutaneous T-cell lymphoma (CTCL) on T cells (TC) in the peripheral blood and its potential role to navigate treatment intervals are explored. METHODS: We investigated within a retrospective monocentric analysis the effect of mogamulizumab on the CD3+ TC and the aberrant T cell population (TCP), i.e., the CD4+ /CD7- and the CD4+ /CD26- TC, analyzed by flow cytometry. RESULTS: Thirteen patients with CTCL were included. After four cycles there was a mean reduction of 57% in CD3+ TC, 72% in the CD4+ /CD7- and 75% in the CD4+ /CD26- TCP compared to the individual baseline of each patient. The reduction in CD4+ /CD7+ and CD4+ /CD26+ TC was lower, averaging 54% and 41%. A significant decrease in aberrant TCP was already evident after the first administration. A median plateau of TCP already occurred during the IP. Progressive disease occurred in 5/13 patients without a clear correlation to aberrant TCP. CONCLUSIONS: Already after one dose of mogamulizumab, aberrant TCP and, to a lesser extent, normal TC decrease. We did not observe a clear correlation between TCP and the efficacy of mogamulizumab, but further studies with larger numbers of patients are needed.

Steroidal saponins from Trillium govanianum as α-amylase, α-glucosidase, and dipeptidyl peptidase IV inhibitory agents.

OBJECTIVE: To provide the scientific basis for the utility of rhizome of Trillium govanianum as nutraceutical supplements in managing physiological glycemic levels. METHODS: The in vitro enzyme inhibitory activity of the extract, fractions, and the isolated steroidal saponins from the rhizome part of T. govanianum was carried out against α-amylase, α-glucosidase, and dipeptidyl peptidase IV. The molecular interactions, binding score, and pharmacokinetic parameters (absorption, distribution metabolism, and excretion) of steroidal saponins were analyzed by the Schrodinger molecular docking software. KEY FINDINGS: Current study explained that the extract, fractions, and isolated steroidal saponins from T. govanianum possess good α-amylase and α-glucosidase inhibitory activity while moderate dipeptidyl peptidase IV inhibitory activity. Moreover, in vitro results revealed that borassoside E (IC50 7.15 ± 1.78 µM), protodioscin (IC50 6.72 ± 0.04 µM), and diosgenin (IC50 12.75 ± 2.70 µM) are most effective in inhibiting the activity of α-amylase, α-glucosidase, and dipeptidyl peptidase IV, respectively. Current in silico and in vitro studies established an association between the steroidal saponins from T. govanianum and their molecular interactions with α-amylase, α-glucosidase, and dipeptidyl peptidase IV. CONCLUSION: The results of this investigation suggest that fractions and steroidal saponins from T. govanianum exhibit good antidiabetic activity which could be used as nutraceutical supplements for the management of systemic glucose level.

Fecal Dipeptidyl Peptidase-4: An Emergent Biomarker in Inflammatory Bowel Disease.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) is a membrane-bound glycoprotein that acts as a receptor but also exists in a soluble form. It has been recognized as a mediator of inflammation and considered a biomarker in inflammatory bowel disease (IBD). METHODS: We evaluated a prospectively recruited cohort, consisting of 101 patients with IBD, using validated clinical indexes; 22 patients with ulcerative colitis (UC) underwent endoscopic evaluation. Fecal DPP-4 (fDPP-4) levels were analyzed and correlated with clinical scores, Mayo endoscopic score (in UC patients), serum DPP-4, C-reactive protein, and fecal calprotectin. Immunohistochemical staining for DPP-4 in intestinal biopsies was also performed. RESULTS: When compared with remitters, median fDPP-4 levels were higher in patients with ileal Crohn's disease (CD) (7,584 [1,464-7,816] vs 2,104 [630-2,676] ng/mL, P = 0.015) and lower in patients with UC exhibiting clinical activity (1,213 [559-1,682] vs 7,814 [2,555-7,985] ng/mL, P < 0.001). Patients with UC presenting endoscopic activity also had lower levels than remitters (939 [559-1,420] vs 7,544 [4,531-7,940] ng/mL, P = 0.006). Fecal DPP-4 discriminated clinical activity from remission with areas under the curve of 0.76 (95% confidence interval [CI] 0.58-0.94, P = 0.015) and 0.80 (95% CI 0.68-0.93, P < 0.001) in CD and UC, respectively; it allowed to differentiate endoscopic activity in patients with UC, with areas under the curve of 0.84 (95% CI 0.63-1.00, P = 0.009). Immunohistochemical analysis revealed higher DPP-4 apical expression in UC remitters, but no statistically significant differences were revealed between patients with ileal CD. DISCUSSION: Our results suggest that fDPP-4 can be used as a biomarker of IBD activity, particularly in UC. The expression profiles in intestinal tissue might represent a functional compartmentalization of DPP-4 expression.

Optimization and validation of a fluorogenic dipeptidyl peptidase 4 enzymatic assay in human plasma.

During the development of a specific dipeptidyl peptidase 4 (DPP4) inhibitor to treat type 2 diabetes, a fluorogenic kinetic analysis for DPP4 enzymatic activity using Gly-Pro-Aminomethylcoumarin (AMC) as a substrate was optimized and validated for recombinant DPP4 and human plasma samples. The sensitivity, calibration curve, detection range, accuracy, precision, recovery efficiency, Km constant, short/long-term stability, and stability after freezing-thawing cycles were analyzed. DPP4 enzymatic activity (mU/min) was measured as the initial velocity (Vo) of the enzymatic reaction over time. The sensitivity of the Vo value was 14,488 mU/min for recombinant DPP4 and 17,995 mU/min for human plasma samples. The dynamic ranges of the calibration curve were linear and reliable between 1.11 × 104-1.86 × 106 mU/min of the mean Vo value and in the DPP4 concentration range of 23.4-3,000 ng/mL. The assay's accuracy and precision met acceptance criteria for all samples. Plasma DPP4 was stable under various storage temperatures, even after three freeze-thaw cycles. Our optimized, validated bioanalytic method for measuring DPP4 activity in plasma samples was successfully employed to evaluate the effect of evogliptin (DA-1229) tartrate, which irreversibly and dose-dependently inhibits DPP4 enzymatic activity, without the dilution effect of human plasma samples and irrespective of the co-treated metformin.

Diabetes y COVID-19 en el adulto mayor, simbiosis nociva / Diabetes and COVID-19 in the elderly, harmful symbiosis

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[Effectiveness of intraperitoneal chemotherapy for t4 colon cancer]. / Effektivnost' vnutribryushnoi khimioterapii pri rake obodochnoi kishki T4.

OBJECTIVE: To determine the effect of intraperitoneal chemotherapy (IPC) with mitomycin C on expression of intraperitoneal cancer cells markers in patients with T4 colon cancer. MATERIAL AND METHODS: For the period from January 2019 to April 2020, 65 patients with T4 colon cancer were included in prospective comparative study. There were 46 patients in the main group and 19 patients in the control group. In the main group, surgical procedure was followed by IPC with mitomycin C. No IPC was performed in the control group. An effectiveness of IPC was evaluated using CD133, CD24, CD26, CD44, CD184 markers expression in peritoneal lavages. RESULTS: Significant between-group differences were observed for CD133 (p=0.0168), CD24 (p=0.0455) and CD44 (p=0.0012). There was a tendency to decrease in the level of CD184 expression in both groups in the second lavage (p=0.0605). CONCLUSION: IPC in patients with T4 colon cancer can reduce the expression and proliferative potential of free cancer cells.

Fabrication of a water-soluble near-infrared fluorescent probe for selective detection and imaging of dipeptidyl peptidase IV in biological systems.

Dipeptidyl peptidase IV (DPP-IV) is a transmembrane glycoprotein known to regulate T cell activation, which is related to various pathological processes and has become a potential target to treat type 2 diabetes mellitus. Therefore, it is significant for the evaluation of endogenous DPP-IV activity in various biological systems. Herein, a water-soluble near-infrared (NIR) fluorescent probe HCA-D based on cyanine dyes as the fluorophore and glycyl-prolyl peptide as the specific recognition sequence was developed for the assay of dipeptidyl peptidase IV (DPP-IV) activity. Upon addition of DPP-IV, HCA-D can emit a significant turn-on NIR fluorescence signal under physiological conditions and exhibit high selectivity toward DPP-IV. This feature was available for quantifying DPP-IV in the range from 0.62 to 10 ng mL-1 with a detection limit of 0.19 ng mL-1. Furthermore, the present probe was successfully employed for monitoring DPP-IV in serum samples from diabetic and healthy people, and imaging of DPP-IV in living cells and tumor mice models. These results demonstrate that the designed probe provides a promising tool to explore the relationship between DPP-IV and diabetes mellitus or other diseases. Perhaps, it may become a prospective image-guided tumor resection indicator based on the abnormal expression of DPP-IV activity in the future.

Identification of Susceptibility Genes to Allergic Rhinitis by Gene Expression Data Sets.

As an extremely prevalent disease worldwide, allergic rhinitis (AR) is a condition characterized by chronic inflammation of the nasal mucosa. To identify the finer molecular mechanisms associated with the AR susceptibility genes, differentially expressed genes (DEGs) in AR were investigated. The DEG expression and clinical data of the GSE19187 data set were used for weighted gene co-expression network analysis (WGCNA). After the modules related to AR had been screened, the genes in the module were extracted for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, whereby the genes enriched in the KEGG pathway were regarded as the pathway-genes. The DEGs in patients with AR were subsequently screened out from GSE19187, and the sensitive genes were identified in GSE18574 in connection with the allergen challenge. Two kinds of genes were compared with the pathway-genes in order to screen the AR susceptibility genes. Receiver operating characteristic (ROC) curve was plotted to evaluate the capability of the susceptibility genes to distinguish the AR state. Based on the WGCNA in the GSE19187 data set, 10 co-expression network modules were identified. The correlation analyses revealed that the yellow module was positively correlated with the disease state of AR. A total of 89 genes were found to be involved in the enrichment of the yellow module pathway. Four genes (CST1, SH2D1B, DPP4, and SLC5A5) were upregulated in AR and sensitive to allergen challenge, whose potentials were further confirmed by ROC curve. Taken together, CST1, SH2D1B, DPP4, and SLC5A5 are susceptibility genes to AR.

Effect of sitagliptin on tubulointerstitial Wnt/ß-catenin signalling in diabetic nephropathy.

AIM: To investigate the effect of sitagliptin on Wnt/ß-catenin signalling in the tubulointerstitium of diabetic nephropathy. METHODS: Forty male Wistar rats were divided into normal control (NC), diabetic model (DM), low and high-dose sitagliptin intervention groups (ST1 and ST2, respectively). Changes in the biochemical parameters and tubulointerstitial fibrosis index were observed. The levels of protein and gene expression of different indicators were detected via immunohistochemistry and real-time polymerase chain reaction. NRK-52E cells were divided into the normal control group, mannitol control group, high glucose group (HG), high glucose plus sitagliptin intervention group (HG + ST) and high glucose plus Wnt/ß-catenin inhibitor group (HG + XAV939). The relevant indicators were examined by Western blot or enzyme-linked immunosorbent assay. RESULTS: Compared with the NC group, the blood glucose, glycosylated haemoglobin, 24 h urinary albumin, creatinine clearance and tubulointerstitial fibrosis index were significantly increased in the DM group. These parameters were decreased in the ST1 and ST2 groups compared to the DM group. Compared with the NC group, the levels of Wnt4, ß-catenin, dipeptidyl peptidase-4 and α-smooth muscle actin were higher and E-cadherin was lower in the DM group. Sitagliptin treatment reversed these changes. In the high glucose-stimulated NRK-52E cells, sitagliptin and XAV939 inhibited the elevated expression of Wnt4, ß-catenin, dipeptidyl peptidase-4, α-smooth muscle actin, transforming growth factor-ß and fibronectin and restored E-cadherin activity. CONCLUSION: Sitagliptin may inhibit the tubulointerstitial Wnt/ß-catenin signalling pathway in diabetic nephropathy and provide renal protection by alleviatinge renal tubulointerstitial transdifferentiation and fibrosis.

Development of novel monoclonal antibodies with specific binding affinity for denatured human CD26 in formalin-fixed paraffin-embedded and decalcified specimens.

A 110-kDa type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region, CD26 has a multitude of biological functions and plays an important role in the regulation of inflammatory responses and tumor biology. Our work has focused on CD26 as a novel therapeutic target for various tumors and immune disorders, and we have recently developed a humanized anti-CD26 monoclonal antibody (mAb), YS110, which has promising safety profile and clinical activity in patients with malignant pleural mesothelioma. The development of an anti-human CD26 mAb that can clearly and reliably detect the denatured CD26 molecule in formalin-fixed paraffin-embedded (FFPE) tissues in the clinical setting is therefore of the utmost importance. To develop novel anti-CD26 mAbs capable of binding to denatured CD26, we immunized mice with urea-treated CD26 protein. Hybridoma supernatants were screened for specific reactivity with human CD26 by immunostaining through the use of a set of FFPE human CD26-positive or negative tumor cell lines. This screening method enables us to develop novel anti-human CD26 mAbs suitable for immunohistochemical staining of CD26 in FFPE non-tumor and tumor tissue sections with reliable clarity and intensity. Specifically, these mAbs display strong binding affinity to denatured human CD26 rather than undenatured human CD26, and are capable of detecting denatured human CD26 in decalcified specimens. These novel anti-CD26 mAbs are potentially useful for the analysis of CD26 expression in cancer patients with bony metastasis, and may help decide the appropriateness of YS110 therapy for future cancer patients.

DPP-4 as a Possible Biomarker of Inflammation Before Abdominal Surgery for Chronic Pathology: Our Experience with Elective Cholecystectomy.

Background and objectives: Dipeptidyl-Peptidase 4 (DPP-4) is a protein expressed in numerous cells and tissues. Recently it has shown its involvement as a catalyst in the inflammatory response in various pulmonary, autoimmune, intestinal and other pathologies. The objective of this study was to compare the preoperative serum levels of DPP-4 in patients with and without surgical finding of perivesicular inflammation. Materials and methods: a cross-sectional analytical study nested in a prospective cohort, including patients scheduled for elective cholecystectomy, without surgical complications, that were 18-70 years of age, with low cardiovascular risk, without a history of peritonitis, pancreatitis, or jaundice and underwent ERCP protocol, type 2 diabetes mellitus, acute inflammatory (Protein C Reactive < 3 mg/L, leucocytes < 10 1000/mm3), neoplastic, nephrologic or liver disease, the use of anti-inflammatory drugs, steroids and/or antibiotics, the use of pacemakers or metallic implants and without major amputations and whom agreed to participate by providing their informed consent. Ethical and Research register: 45-16. Prior to surgery we compiled anthropometric data and a blood sample to determine the serum levels of DPP-4. The presence of perivesicular inflammation was determined in the surgery. The data was analyzed using the statistical program Rstudio. Results: High BMI values were observed (27.8 ± 6.4); waist circumference (94.7 ± 15.1) and percentage of fat mass (34.7 ± 11.7), showing a cumulative frequency of 65.9% for overweight/obesity. In 27.3% of the interventions, intraoperative perivesicular inflammation findings were reported. The serum levels of DPP-4 were lower in the group of patients with perivesicular inflammation (3947.6 ± 1659.5 vs. 3053.2 ± 1469.6, LC95% of the difference: 160.4-1628.3), being statistically significant (P = 0.018). Conclusions: In the subacute or chronic phases of cholecystitis, there appears to be a constant consumption of DPP-4, which would modulate a better immune response that could be related to the reduction of postoperative complications, so the use of Serum levels of DPP-4 as an early biomarker could improve the diagnostic accuracy of this pathology and the surgical approach.

Neuropeptide Y and dipeptidyl peptidase IV in normally cycling and postmenopausal women: A prospective pilot study.

The purpose was to investigate changes in neuropeptide Y (NPY) protein and dipeptidyl peptidase IV (DPP-IV) activity in the plasma and saliva in normally cycling women and women after menopause. We recruited 7 cycling women and 7 postmenopausal women for a cross-sectional, prospective pilot study. Blood via venipuncture and saliva samples were taken at each point in the menstrual cycle (premenopausal) or once per week (postmenopausal) for 2 months. Blood and saliva were analyzed for estrogen, NPY using ELISA and DPP-IV activity using a fluorometric assay. Plasma ß-estradiol was an average of 96.45 ±â€Š57.04 pg/mL over 2 cycles in the premenopausal group and 1.72 ±â€Š0.35 pg/mL over 2 months in the postmenopausal group (P < .05). In the cycling group, there were no significant differences in saliva or plasma NPY or DPP-IV over the cycle. For the postmenopausal group, salivary NPY and DPP-IV did not change over 2 months. Plasma NPY was lowest in the middle 2 weeks (average: 0.52 ±â€Š0.10 ng/mL) compared to the first and fourth weeks (average of week 1 and 4: 0.60 ±â€Š0.14 ng/mL; P < .05). Plasma NPY in postmenopausal women was higher overall (0.56 ±â€Š0.13 ng/mL) compared to cycling women (0.30 ±â€Š0.11 ng/mL; P < .05). Plasma DPP-IV activity was unchanged by time in the postmenopausal group. Saliva DPP-IV and saliva NPY in the cycling group had a significant negative correlation (R = -0.95; P < .05). We found that saliva measures of NPY and DPP-IV activity appear to be poor estimates of plasma concentrations and activities, but a larger sample size is required to conform this. Differences in plasma NPY concentrations between the groups and the relationship between salivary NPY and DPP-IV suggests that there may be some unique differences between these groups.

A Universal Assay for Aminopeptidase Activity and Its Application for Dipeptidyl Peptidase-4 Drug Discovery.

Aminopeptidases, such as dipeptidyl peptidase-4 (DPP-4, CD26), are potent therapeutic targets for pharmacological interventions because they play key roles in many important pathological pathways. To analyze aminopeptidase activity in vitro (including high-throughput screening [HTS]), in vivo, and ex vivo, we developed a highly sensitive and quantitative bioluminescence-based readout method. We successfully applied this method to screening drugs with potential DPP-4 inhibitory activity. Using this method, we found that cancer drug mitoxantrone possesses significant DPP-4 inhibitory activity both in vitro and in vivo. The pharmacophore of mitoxantrone was further investigated by testing a variety of its structural analogues.

Hollow-Core-Photonic-Crystal-Fiber-Based Miniaturized Sensor for the Detection of Aggregation-Induced-Emission Molecules.

A miniature sensor for detection of aggregation-induced-emission (AIE) molecules is proposed in this work. The sensing head is fabricated by use of hollow-core photonic crystal fiber with a core diameter of about 4.8 µm. The cladding holes are sealed with a fusion splicing technique, and the central hole remains open to allow the filtration of solution with AIE molecules. When the solution is excited by an ultraviolet lamp, the fluorescence is received by a fiber-optic spectrometer. The fluorescence intensity is associated with the concentration of AIE molecules and the infiltrated-core length. In the whole process of the experiments, the output-peak wavelength is stable, which indicates that the existing forms of AIE particles are stable, and the fluorescence reabsorption can be neglected. The experimental results obtained are in accordance with traditional microplate-spectrophotometer methods. The most exciting result is that the amount of sample measured can be as low as 0.36 nL, which allows the detection of AIE molecules at only 0.02 pmol. In addition, the miniature sensor was successfully applied to the detection of an AIE-based bioprobe for evaluating the activity of the dipeptidyl-peptidase 4 (DPP-4) inhibitor sitagliptin with an IC50 of 59.80 ± 3.06 nM. The advantages of small device size and nanoliter-scale sample volumes suggest that the proposed sensor is promising for many biosensing applications.

A novel non-enzymatic hydrolytic probe for dipeptidyl peptidase IV specific recognition and imaging.

A novel non-enzymatic hydrolytic probe for DPP IV is obtained. And this new probe can be used for special DPP IV recognition and imaging in living cells. Importantly, one general strategy for the construction of new non-enzymatic fluorescent probes for many important proteases can be proposed based on the present study.

Activatable Near-Infrared Fluorescent Probe for Dipeptidyl Peptidase IV and Its Bioimaging Applications in Living Cells and Animals.

Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.

Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus.

Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76 ±â€¯108.06 ng/ml) was significantly lower than those of healthy controls (703.42 ±â€¯169.96 ng/ml), but there were no significant differences among the patient groups. Interestingly, plasma levels of IL-10 and EGF were negatively and positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels in sputa were less than 300 ng/ml. Viral infection was inhibited by 50% in the presence of more than 8000 ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma of MERS patients are significantly reduced below the threshold needed to exert an antiviral effect against MERS-CoV infection.

The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of Polistes dominula venom.

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

Comparative analysis of proteomes between diabetic and normal human sperm: Insights into the effects of diabetes on male reproduction based on the regulation of mitochondria-related proteins.

This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1.2 or <0.83). According to gene ontology enrichment and pathway analyses, many of these differentially expressed proteins are associated with sperm function, including binding of sperm to the zona pellucida and proteasome function; of particular interest, half of these proteins were related to mitochondrial metabolism. Protein-interaction networks revealed that a decrease in Cystatin C and Dipeptidyl peptidase 4 in the mitochondria may be sources of the decreased motility of sperm from diabetic patients.