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Journal of Dairy Science Feb 2024Cows in early lactation (EL) are purportedly immune suppressed, which renders them more susceptible to disease. Thus, the study objective was to compare key biomarkers...
Cows in early lactation (EL) are purportedly immune suppressed, which renders them more susceptible to disease. Thus, the study objective was to compare key biomarkers of immune activation from i.v. lipopolysaccharide (LPS) between EL and mid-lactation (ML) cows. Multiparous EL (20 ± 2 DIM; n = 11) and ML (131 ± 31 DIM; n = 12) cows were enrolled in a 2 × 2 factorial design and assigned to 1 of 2 treatments by lactation stage (LS): (1) EL (EL-LPS; n = 6) or ML (ML-LPS; n = 6) cows administered a single LPS bolus from Escherichia coli O55:B5 (0.09 µg/kg of body weight), or (2) pair-fed (PF) EL (EL-PF; n = 5) or ML (ML-PF; n = 6) cows administered i.v. saline. After LPS administration, cows were intensely evaluated for 3 d to analyze their response and recovery to LPS. Rectal temperature increased in LPS relative to PF cows (1.1°C in the first 9 h), and the response was more severe in EL-LPS relative to ML-LPS cows (2.3 vs. 1.3°C increase at 4 h post-LPS; respectively). Respiration rate increased only in EL-LPS cows (47% relative to ML-LPS in the first h post-LPS). Circulating tumor necrosis factor-α, IL-6, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and IFN-γ-inducible protein-10 increased within the first 6 h after LPS and these changes were exacerbated in EL-LPS relative to ML-LPS cows (6.3-, 4.8-fold, 57%, 93%, 10%, and 61% respectively). All cows administered LPS had decreased circulating iCa relative to PF cows (34% at the 6 h nadir), but the hypocalcemia was more severe in EL-LPS than ML-LPS cows (14% at 6 h nadir). In response to LPS, neutrophils decreased regardless of LS, then increased into neutrophilia by 24 h in all LPS relative to PF cows (2-fold); however, the neutrophilic phase was augmented in EL- compared with ML-LPS cows (63% from 24 to 72 h). Lymphocytes and monocytes rapidly decreased then gradually returned to baseline in LPS cows regardless of LS; however, monocytes were increased (57%) at 72 h in EL-LPS relative to ML-LPS cows. Platelets were reduced (46%) in LPS relative to PF cows throughout the 3-d following LPS, and from 24 to 48 h, platelets were further decreased (41%) in EL-LPS compared with ML-LPS. During the 3-d following LPS, serum amyloid A (SAA), LPS-binding protein (LBP), and haptoglobin (Hp) increased in LPS compared with PF groups (9-fold, 72%, and 153-fold, respectively), and the LBP and Hp responses were more exaggerated in EL-LPS than ML-LPS cows (85 and 79%, respectively) whereas the SAA response did not differ by LS. Thus, our data indicates that EL immune function does not appear "suppressed," and in fact many aspects of the immune response are seemingly functionally robust.
PubMed: 38428491
DOI: 10.3168/jds.2023-24350 -
European Journal of Gastroenterology &... Apr 2024Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of...
Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.
BACKGROUND
Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction.
METHODS
Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics.
RESULTS
Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD).
CONCLUSION
Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Induction Chemotherapy; Tumor Necrosis Factor-alpha; Patient Reported Outcome Measures; Gastrointestinal Agents; Treatment Outcome; Remission Induction; Antibodies, Monoclonal, Humanized
PubMed: 38417060
DOI: 10.1097/MEG.0000000000002728 -
Frontiers in Microbiology 2024This study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last...
INTRODUCTION
This study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last 60 days of gestation.
METHODS
Fifteen pregnant DeZhou donkeys with age of 6.0 ± 0.1 years, body weight of 292 ± 33 kg, parity of 2.7 ± 0.1 parities and similar expected date of confinement (74 ± 4 days) were randomly allocated to three groups and feed three diets: high energy (10.92 MJ/kg, H), medium energy (10.49 MJ/kg, M), and low energy (9.94 MJ/kg, L).
RESULTS AND DISCUSSION
The serum activity of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in group M was significantly higher, whereas the concentrations of malondialdehyde (MDA), interleukin 1 (IL-1), IL-2, and IL-6 were lower than those recorded for groups H and L ( ≤ 0.05). The dietary energy level significantly affected rectal microbial community structure in the jennet donkeys 35 days and 7 days before the parturition ( ≤ 0.05). The abundances of genus was significantly higher ( ≤ 0.05) in group H, and the abundances of and the were higher in group L ( ≤ 0.05). The abundance of Fibrobacter in group M was significantly increased ( ≤ 0.05). The abundance of was positively correlated with average daily gain (ADG) and tumor necrosis factor-α (TNF-α) concentrations ( ≤ 0.05). The abundance of was positively correlated with IL-2 and IL-6 concentrations. The abundance of was positively correlated with CAT, T-SOD and GSH-Px activities ( ≤ 0.05). The abundance of Fibrobacter was positively correlated with CAT and T-SOD activities ( ≤ 0.05), but negatively correlated with IL-2 concentration ( ≤ 0.05). In conclusion, an appropriate dietary with an energy content of 10.49 MJ/kg for jennet donkeys during late gestation increased the prenatal antioxidant capacity, reduced inflammatory cytokines, and promoted fetal growth, and these changes were related to diet-induced changes in rectal microbiota compositions.
PubMed: 38414765
DOI: 10.3389/fmicb.2024.1308171 -
Metabolites Feb 2024This study aimed to determine whether heat stress affected the values and correlations of metabolic, endocrinological, and inflammatory parameters as well as the rectal...
This study aimed to determine whether heat stress affected the values and correlations of metabolic, endocrinological, and inflammatory parameters as well as the rectal and body surface temperature of cows in the early and middle stages of lactation. This experiment was conducted in May (thermoneutral period), June (mild heat stress), and July (moderate to severe heat stress). In each period we included 15 cows in early lactation and 15 in mid-lactation. The increase in rectal and body surface temperatures (°C) in moderate to severe heat stress compared to the thermoneutral period in different regions was significant ( < 0.01) and the results are presented as mean and [95%CI]: rectal + 0.9 [0.81-1.02], eye + 6 [5.74-6.25], ear + 13 [11.9-14.0], nose + 3.5 [3.22-3.71], forehead + 6.6 [6.43-6.75], whole head + 7.5 [7.36-7.68], abdomen + 8.5 [8.25-8.77], udder + 7.5 [7.38-7.65], front limb + 6 [5.89-6.12], hind limb + 3.6 [3.46-3.72], and whole body + 9 [8.80-9.21]. During heat stress (in both mild and moderate to severe stress compared to a thermoneutral period), an increase in the values of extracellular heat shock protein 70 (eHsp70), tumor necrosis factor α (TNFα), cortisol (CORT), insulin (INS), revised quantitative insulin sensitivity check index (RQUICKI), urea, creatinine, total bilirubin, aspartate transpaminase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and creatin kinase (CK) occurred, as well as a decrease in the values of triiodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA), glucose (GLU), β-Hydroxybutyrate (BHB), calcium, phosphorus, total protein (TPROT), albumin (ALB), triglycerides (TGCs), and cholesterol (CHOL). In cows in early lactation compared to cows in mid-lactation, there was a significantly larger increase ( < 0.01) in the values of eHsp70, TNFα, GLU, RQUICKI, and GGT, while the INS increase was smaller during the three experimental periods. The decrease in the values of Ca, CHOL, and TGC was more pronounced in cows in early lactation compared to cows in mid-lactation during the three experimental periods. Rectal temperature was related to eHsp70 (r = 0.38, < 0.001) and TNFα (r = 0.36, < 0.01) and showed non-significant poor correlations with other blood parameters. Blood parameters correlate with body surface temperature, with the following most common results: eHsp70 and TNFα showed a moderately to strongly significant positive correlation (r = 0.79-0.96, < 0.001); CORT, INS, and Creat showed fairly to moderately significant positive correlations; T3, T4, NEFA and GLU showed fairly to moderately significant negative correlations (r = 0.3-0.79; < 0.01); RQUICKI, urea, AST, and GGT showed fairly and significantly positive correlations; and TGC, CHOL, TPROT, and ALB showed fairly and significantly negative correlations (r = 0.3-0.59; < 0.01). Measuring the surface temperature of the whole body or head can be a useful tool in evaluating the metabolic response of cows because it has demonstrated an association with inflammation (TNFα, eHsp70), endocrine response (CORT, T3, T4), the increased use of glucose and decreased use of lipids for energy purposes (INS, NEFA, GLU, and RQUICKI), and protein catabolism (ALB, TPROT, urea, Creat), which underlies thermolysis and thermogenesis in cows under heat stress. In future research, it is necessary to examine the causality between body surface area and metabolic parameters.
PubMed: 38392996
DOI: 10.3390/metabo14020104 -
International Journal of Molecular... Jan 2024Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to... (Meta-Analysis)
Meta-Analysis
Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory genes in treatment-naïve pediatric patients with UC. Using the Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) platform and R algorithms, we analyzed rectal biopsy transcriptomic data from two cohorts (206 patients with UC vs. 20 healthy controls from the GSE-109142 study, and 43 patients with UC vs. 55 healthy controls from the GSE-117993 study). We compared gene expression levels and correlation of clock genes (, , , , , ), inflammatory genes (, , , , , ) and their mutual regulatory genes (, , , , , , , ) in patients with active UC and healthy controls. The clock genes , , and and the inflammatory genes , , , , and were significantly upregulated in patients with active UC. The genes encoding the mutual regulators , , , and were significantly downregulated in patients with UC. A uniform pattern of gene expression was found in healthy controls compared to the highly variable expression pattern in patients with UC. Among the healthy controls, inflammatory genes were positively correlated with clock genes and they all showed reduced expression. The difference in gene expression levels was associated with disease severity and endoscopic score but not with histological score. In patients with active UC, clock gene disruption is associated with abnormal mucosal immune response. Disrupted expression of genes encoding clock, inflammation and their mutual regulators together may play a role in active UC.
Topics: Child; Humans; ARNTL Transcription Factors; Circadian Rhythm; Colitis, Ulcerative; Inflammation; Interleukin-10; Interleukin-6; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR alpha; PPAR gamma; Tumor Necrosis Factor-alpha; CLOCK Proteins; Period Circadian Proteins; Cryptochromes
PubMed: 38338765
DOI: 10.3390/ijms25031488 -
Animals : An Open Access Journal From... Feb 2024Cold conditions in northern China during winter may reduce sheep growth and affect their health, especially if they are young, unless housing is provided. We allocated...
Cold conditions in northern China during winter may reduce sheep growth and affect their health, especially if they are young, unless housing is provided. We allocated 45 two-month-old female lambs to be housed in an enclosed building, a polytunnel, or kept outdoors, for 28 days. The daily weight gain and scalp and ear skin temperature of outdoor lambs were less than those of lambs that were housed in either a house or polytunnel; however, rectal temperature was unaffected by treatment. There was a progressive change in blood composition over time, and by the end of the experiment, outdoor lambs had reduced total antioxidant capacity (T-AOC), catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) and increased malondialdehyde compared to those in the house or polytunnel. In relation to immune responses in the lambs' serum, in the polytunnel, immunoglobulin A (IgA), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were higher and immunoglobulin G (IgG) lower compared with the concentrations in lambs that were outdoors. Over the course of the experiment, genes expressing heat shock proteins and antioxidant enzymes increased in lambs in the outdoor treatment, whereas they decreased in lambs in the indoor treatments. It is concluded that although there were no treatment effects on core body temperature, the trends for progressive changes in blood composition and gene expression indicate that the outdoor lambs were not physiologically stable; hence, they should not be kept outdoors in these environmental conditions for long periods.
PubMed: 38338161
DOI: 10.3390/ani14030518 -
Revista Espanola de Enfermedades... Feb 2024Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and...
Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and management are essential to avoid serious complications. The case of a patient with Ogilvie syndrome refractory to medical and endoscopic treatment that required surgery is presented. This is a 68-year-old man with decreased level of consciousness and abdominal distension for 3 days. Last bowel movement 4 days ago. The data and tests appear in table 1. We are faced with a patient with neurological alteration and hemodynamically unstable secondary to complicated Ogilvie syndrome. After admission to the ICU, where a 2.5 mg bolus of neostigmine was administered, he was transferred to the ward. Despite 250 mg of intravenous erythromycin every 6 hours together with metoclopramide every 8 hours, high doses of polyethylene glycol and daily cleansing enemas and rectal catheterization, only a brief and mild improvement is achieved. Given the failure of conservative measures, colectomy was performed, achieving complete resolution. Ogilvie syndrome is a functional disorder1 that usually associates predisposing factors that impact intestinal motility 2 ; In our case: bedridden, the use of anticholinergics, hydroelectric alteration both due to the use of antidepressants and the creation of a third space secondary to colonic dilation and severe intestinal ischemia². In one third it is resolved by early correction of the triggering factors, adding neostigmine if necessary with high rates of effectiveness¹. In our case, a second bolus of neostigmine could have been administered or even as an infusion since greater efficacy has been demonstrated in this way given its short half-life². Electrolyte imbalance is a predictor of poor response to neostigmine, a factor that was associated with our patient 3. Colonic decompression and finally surgery are reserved as a last measure, being necessary in a very small percentage as in this case 1. As a preventive measure, the administration of 29.5 g of oral polyethylene glycol per day has been effective 4. Therefore, we should suspect Ogilvie syndrome in patients with predisposing factors who present acute dilation of the colon without mechanical obstruction, and although it usually resolves with medical and endoscopic treatment, we should not delay surgery to avoid complications.
PubMed: 38305678
DOI: 10.17235/reed.2024.10287/2024 -
Cureus Dec 2023Colorectal cancer is a common malignancy, with the liver being the most frequent site of metastases. [F] Fluorodeoxyglucose ([F]FDG) positron emission...
Colorectal cancer is a common malignancy, with the liver being the most frequent site of metastases. [F] Fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) has emerged as a valuable tool in detecting and evaluating liver metastases and extrahepatic disease. Herein, we present a case of a 76-year-old male with colorectal cancer associated with lung and liver metastases. The patient received 12 chemoimmunotherapy cycles and was then put on maintenance cetuximab; serial [F]FDG PET/CT scans were utilized to evaluate treatment response. The patient exhibited a positive response to chemoimmunotherapy, with regression of rectal disease and resolution of pulmonary metastatic nodules. Serial [F]FDG PET/CT scans unveiled three distinct necrotic patterns. The case report advocates that [F]FDG PET/CT plays an important role in evaluating colorectal liver metastases (CRLM) response to treatment, identifying transient necrosis, early recurrence, and emphasizing the limitations of post-treatment CT scans in identifying early CRLM recurrence. Integrating functional imaging, particularly [F]FDG PET/CT, promises for management monitoring and surveillance of CRLM patients.
PubMed: 38292976
DOI: 10.7759/cureus.51393 -
Journal of Translational Medicine Jan 2024Inflammatory Bowel Diseases (IBD), an autoimmune disease characterised by abnormal intestinal immunity, are related to vital morbidity around the world. However,...
BACKGROUND
Inflammatory Bowel Diseases (IBD), an autoimmune disease characterised by abnormal intestinal immunity, are related to vital morbidity around the world. However, therapeutic agents for IBD have not achieved desired benefit. Exploring new therapeutic targets for IBD, especially based on its abnormally intestinal immunity, could alleviate the flare-up and worsening of IBD. Tissue resident memory T cells (TRM) are core of multiple autoimmune diseases, including IBD. However, the mechanism of TRM differentiation remains to be investigated.
METHODS
The alterations in mRNA and lncRNA profile of intestinal intraepithelial lymphocytes (IELs), the largest component of intestinal TRM, were analyzed in DSS-induced chronic colitis. Based on it, we examined the function of rectal insulin instillation in a dextran sodium sulfate (DSS) induced chronic colitis. Furthermore, we investigated the downstream-target of the insulin pathway-EZH2 and the crucial role of EZH2 in intestinal tissue resident memory T cell differentiation by utilizing EZH2CD4 mice.
RESULTS
Insulin receptor (INSR) expression was found to be significantly reduced. Activation of mucosal insulin pathway by rectal insulin instillation exacerbated colitis by disrupting IELs subgroups and up-regulating TNF-ɑ and IL-17 expression. Rectal insulin instillation promoted EZH2 expression and EZH2 inhibition alleviated chronic colitis. EZH2CD4 mice restored the normal IEL subgroups and suppressed TNF-ɑ and IL-17 expression, exhibiting alleviated colitis. IELs from EZH2CD4 mice exhibit significant changes in TRM related phenotype. CD4TRM was significantly increased in chronic colitis and decreased in EZH2CD4 mice.
CONCLUSION
Insulin receptor of intestinal mucosal T-cells could promote intestinal TRM differentiation via EZH2. Our discoveries suggest that therapies targeting colonic INSR and EZH2 could be potential treatment for IBD based on its regulatory effects on TRM. Insulin receptor inhibitors rather than insulin should be applied during colitis-active phase. In addition, EZH2 shows to be a downstream signal of the insulin pathway and EZH2 inhibitor could alleviating intestinal inflammation. However, the critical role of EZH2 in TRM differentiation restricts the anti-tumor effects of EZH2 inhibitor in vivo.
Topics: Mice; Animals; Interleukin-17; Tumor Necrosis Factor-alpha; Receptor, Insulin; Memory T Cells; Colitis; Inflammatory Bowel Diseases; Cell Differentiation; Intestinal Mucosa; Inflammation; Insulins; Dextran Sulfate; Disease Models, Animal
PubMed: 38243324
DOI: 10.1186/s12967-023-04789-x