As the demand for alternatives to antibiotic growth promoters (AGP) increases in food animal production, phytobiotic compounds gain popularity because of their ability to mimic the desirable ...bioactive properties of AGP. Chestnut tannins (ChT) are one of many phytobiotic compounds used as feed additives, particularly in South America, for broilers because of its favorable antimicrobial and growth promotion capabilities. Although studies have observed the microbiological and immunologic effects of ChT, there is a lack of studies evaluating the metabolic function of ChT. Therefore, the objective of this study was to characterize the cecal metabolic changes induced by ChT inclusion and how they relate to growth promotion. A total of 200 day-of-hatch broiler chicks were separated into 2 feed treatment groups: control and 1% ChT. The ceca from all the chicks in the treatment groups were collected on day 2, 4, 6, 8, and 10 after hatch. The cytokine mRNA quantitative RT-PCR was determined using TaqMan gene expression assays for IL-1B, IL-6, IL-8, IL-10, and interferon gamma quantification. The cytokine expression showed highly significant increased expressions of IL-6 and IL-10 on day 2 and 6, whereas the other proinflammatory cytokines did not have significantly increased expression. The results from the kinome array demonstrated that the ceca from birds fed with 1% ChT had significant (P < 0.05) metabolic alterations based on the number of peptides when compared with the control group across all day tested. The increased expression of IL-6 appeared to be strongly indicative of altered metabolism, whereas the increased expression of IL-10 indicated the regulatory effect against other proinflammatory cytokines other than IL-6. The ChT initiate a metabolic mechanism during the first 10 d in the broiler. For the first time, we show that a phytobiotic product initially modulates metabolism while also potentially supporting growth and feed efficiency downstream. In conclusion, a metabolic phenotype alteration in the ceca of chickens fed ChT may indicate the importance of enhanced broiler gut health.
Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in ...rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163+ , SWC3a+ , CD4a+ , and CD8a+ cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion−induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.
Delayed graft function (DGF) leads to a reduced graft survival. Donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the ...recipients' characteristics in the development of DGF.
We enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples.
In the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C-C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients.
Our results suggest that recipients' clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors' features.
The Role of MUC1 in Renal Cell Carcinoma Milella, Martina; Rutigliano, Monica; Lasorsa, Francesco ...
Biomolecules (Basel, Switzerland),
03/2024, Letnik:
14, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, ...and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.
Six food-grade tannins obtained from different woods were used as a source of polyphenolic compounds at two concentrations (0.5% and 1%
/
) in yogurt formulations and monitored during 3 weeks of ...storage. Yogurt containing tannins showed significantly higher total phenolic content (+200%), antioxidant activity (+400%), and syneresis (+100%) than control. These changes were higher with fortification at 1%. Tannin origin also significantly influenced the yogurt composition and yogurt obtained from a Turkish gall showed higher values of total phenolic content (4 mg GAE/g) and antioxidant activity (17 μM Trolox/g). Yogurt color was evaluated by CIELab parameters, and their values were influenced by tannin origin and concentration. The addition of tannins did not significantly affect the number of lactic acid bacteria. Yogurt with a lower amount of tannins (0.5%
/
) received higher consumer acceptability but significant differences in preferences were due to tannin origin. In particular, yogurt added with tannin obtained from Quebracho wood at 1%
/
showed higher consumer preference. The obtained results would provide an opportunity for dairy producers to develop a novel dairy food with high nutritional quality.
Neuraxial anesthesia (NA) showed to reduce both morbidity and mortality in patients undergoing laparoscopic surgery. We aimed to investigate the use of NA in patients undergoing transperitoneal ...three-dimensional laparoscopic radical prostatectomy (t-3DLRP) and compare the intraoperative and postoperative outcomes with a control group of patients undergoing t-3DLRP under general anesthesia (GA).
A prospective, double-center, double-surgeon study cohort of 84 consecutive patients undergoing t-3DLRP between June 2019 and June 2021 was analyzed. A study group of 42 patients undergoing t-3DLRP under NA was compared with a control group of 42 patients undergoing t-3DLRP under GA.
The two group were similar in all demographic, clinical, and pathological variables. Postoperative blood gas parameters were within physiologic limits in both groups. Muscle relaxation was adequate for surgery during both NA and GA. Median length of stay was 1 day shorter for NA group than GA group (5 days vs. 6 days, p=0.05). t-3DLRP under NA had a statistically lower rate of minor complications (4.8% vs. 19.0%, p=0.03) and less postoperative pain (median numeric rating scale 3 vs. 4, p=0.01) compared to GA. No major complications were observed in both groups. Significantly more patients were willing to undergo a similar intervention under NA than GA (p=0.04).
t-3DLRP under NA is a feasible and safe procedure, with less postoperative pain and fewer minor complications than the same procedure under GA. NA allows the maintenance of muscle relaxation and respiratory excursions without interfering with surgery.
Chronic allograft nephropathy (CAN) represents the main cause of renal allograft loss after 1 yr of transplantation. Calcineurin inhibitor (CNI) use is associated with increased graft expression of ...profibrotic cytokines, whereas rapamycin inhibits fibroblast proliferation. The aim of this randomized, prospective, open-label, single-center study was to evaluate the histologic and clinical effect of rapamycin on biopsy-proven CAN. Eighty-four consecutive patients who had biopsy-proven CAN and received a transplant were randomized to receive either a 40% CNI reduction plus mycophenolate mofetil (group 1; 50 patients) or immediate CNI withdrawal and rapamycin introduction with a loading dose of 0.1 mg/kg per d and a maintaining dose aiming at through levels of 6 to 10 ng/ml (group 2; 34 patients). The follow-up period was 24 mo. At the end of follow-up, 25 patients (group 1, 10 patients; group 2, 15 patients) underwent a second biopsy. CAN lesions were graded according to Banff criteria. alpha-Smooth muscle actin (alpha-SMA) protein expression was evaluated in all biopsies as a marker of fibroblast activation. Graft function and Banff grading were superimposable at randomization. Graft survival was significantly better in group 2 (P = 0.0376, chi2 = 4.323). CAN grading worsened significantly in group 1, whereas it remained stable in group 2. After 24 mo, all group 1 biopsies showed an increase of alpha-SMA expression at the interstitial and vascular levels (P < 0.001); on the contrary, alpha-SMA expression was dramatically reduced in group 2 biopsies (P = 0.005). This study demonstrates that rapamycin introduction/CNI withdrawal improves graft survival and reduces interstitial and vascular alpha-SMA expression, slowing down the progression of allograft injury in patients with CAN.
The objective of this study was to identify the phosphorylation events associated with host immunity with the inclusion of chestnut tannins (ChT) in the diet. A total of 200 male day-of-hatch Cobb ...500 chicks were randomly assigned to two treatment groups, totaling 50 chicks per pen per experiment (this study was repeated two times). The treatments were as follows: (1) control feed-normal starter feed (n = 50), and (2) 1% ChT inclusion feed (n = 50). The ceca were collected on each necropsy day for analysis via (1) a peptide array to provide tissue immunometabolism information from the host, and (2) quantitative PCR for mRNA expression. Of the top three immune pathways, the data identified the T-cell receptor signaling pathway, the chemokine signaling pathway, and the JAK-STAT signaling pathway. The results showed significantly altered phosphorylation of JAK and STAT peptides within the JAK-STAT pathway. These results support the mRNA expression data with the upregulated IL-6 response, due to the significant phosphorylation of IL6ST, JAK, and STAT peptides. In regard to immune modulation, ChT appear to influence host immunity via an IL-6 mediated response which could be beneficial in host defenses against pathogens at the early stages of broiler growth and development. Therefore, it is suggested that the role of the JAK-STAT pathway is altered by including ChT in the diet.
Background:
Anticancer treatments can impair male fertility. Cryopreservation of semen is an efficient procedure for fertility preservation. The aim of this study was to evaluate pre-freeze semen ...parameters among the various types of cancer, post-thaw sperm viability and reproductive outcome of samples used for assisted reproductive treatment (ART).
Methods:
This study included 721 men with cancer that had their semen cryopreserved in our bank in 1999–2015. Semen analysis and cryopreservation were performed before the start of antineoplastic treatment, according to the World Health Organization recommendations, European Commission and Italian law.
Results:
Among the 721 patient, 196 had seminoma of the testis, 173 Hodgkin’s lymphoma, 108 mixed testicular tumors, 89 germ cell tumors, 67 other tumors, 46 hematological tumors, and 42 non-Hodgkin’s lymphoma. The mean age of patients was significantly lower in Hodgkin’s lymphoma compared to other tumors. Statistically significant lower volume, sperm count and number of straws stored were observed respectively in Hodgkin’s lymphoma, mixed testicular tumor and hematological tumors. Nineteen patients used their frozen semen for 20 ART cycles. After thawing a significant reduction of motility and vitality was recorded. A lower fertilization rate was observed in patients affected by testicular tumor and lymphoma (35.42% and 50%) compared with other cancers (71.43%). No significant differences were observed in terms of cleavage and implantation rates. A total of five pregnancies and seven healthy newborns were achieved.
Conclusions:
Fertility preservation before gonadotoxic therapy is of great importance to patients with cancer and must be indicate before the start of treatment.
Clear cell renal cell carcinoma (ccRCC) is the most common malignant renal epithelial tumor and also the most deadly. To identify molecular changes occurring in ccRCC, in the present study we ...performed a genome wide analysis of its entire complement of mRNAs. Gene and exon-level analyses were carried out by means of the Affymetrix Exon Array platform. To achieve a reliable detection of differentially expressed cassette exons we implemented a novel methodology that considered contiguous combinations of exon triplets and candidate differentially expressed cassette exons were identified when the expression level was significantly different only in the central exon of the triplet. More detailed analyses were performed for selected genes using quantitative RT-PCR and confocal laser scanning microscopy. Our analysis detected over 2,000 differentially expressed genes, and about 250 genes alternatively spliced and showed differential inclusion of specific cassette exons comparing tumor and non-tumoral tissues. We demonstrated the presence in ccRCC of an altered expression of the PTP4A3, LAMA4, KCNJ1 and TCF21 genes (at both transcript and protein level). Furthermore, we confirmed, at the mRNA level, the involvement of CAV2 and SFRP genes that have previously been identified. At exon level, among potential candidates we validated a differentially included cassette exon in DAB2 gene with a significant increase of DAB2 p96 splice variant as compared to the p67 isoform. Based on the results obtained, and their robustness according to both statistical analysis and literature surveys, we believe that a combination of gene/isoform expression signature may remarkably contribute, after suitable validation, to a more effective and reliable definition of molecular biomarkers for ccRCC early diagnosis, prognosis and prediction of therapeutic response.
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