Improved tenderness of beef from bulls supplemented with active dry yeast is related to matrix metalloproteinases and reduced oxidative stress

To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. Research unit at university hospital. Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.

This study was conducted to compare the effect of active dry yeasts (ADY) and yeast cultures (YC), two typical products of yeast preparations, on ruminal fermentation parameters, and on the fatty acid composition and flavour of beef from finishing bulls fed a high-concentrate diet. Forty-five finishing bulls (mean bodyweight ± s.d.: 505.4 ± 29.1 kg body weight) were allocated to three groups of 15 bulls and assigned randomly to one of three diets, which were CON diet (basal diet), ADY diet (basal diet + Levucell SC) and YC diet (basal diet + Diamond V XP). After 112 days trial, all bulls (mean bodyweight ± s.d.: 591.6 ± 64.2 kg body weight) were slaughtered. The rumen fluid of each animal was collected at slaughter and cross-sectional samples of longissimus lumborum were collected from three treatments at carcass segmentation after a 24-h chill. The result indicated that both ADY and YC supplementation had no significant effect (P > 0.05) on rumen pH, concentration of ammonia-N and total volatile fatty acid compared with CON. ADY had no significant effect (P > 0.05) on percentage of rumen individual fatty acid whereas YC significantly decreased valerate molar percentage (P = 0.008) and increased acetate molar percentage (P = 0.029) and the ratio of acetate to propionate (P = 0.035). In addition, compared with CON, ADY significantly (P = 0.003) increased the concentration of C16:1n7 and significantly (P = 0.012) decreased the concentration of C18:3n6c compared with CON. YC significantly decreased the concentration of C18:3n6c (P = 0.014) compared with CON. However, both ADY and YC had no significant effect (P > 0.05) on other individual fatty acid concentrations, the proportions of saturated fatty acids and monounsaturated fatty acids and nutritionally important values including the ratio of n-6/n-3, polyunsaturated fatty acids/saturated fatty acid and C18:2n6/C:18:3n3. Both ADY and YC significantly improved beef tenderness for cooking method of chaffy dish (P < 0.05) and beef tenderness also tended improve for ADY (P = 0.075) and YC (P = 0.097) when samples were fried. Both ADY and YC did not show improvements in flavour or juiciness compared with CON for either cooking method.

Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1β, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H2O2 were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H2O2 had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.

BackgroundCardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and −9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs.MethodsA total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits.ResultsSerum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (rs = 0.208, p < 0.001 for MMP-2; rs = 0.163, p < 0.01 for MMP-9), hair (rs = 0.163, p < 0.01 for MMP-2; rs = 0.173, p < 0.01 for MMP-9) and nail (rs = 0.160, p < 0.01 for MMP-2; rs = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 μg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs.ConclusionsThis study showed the significant positive associations and dose–response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.

Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB.

Previous studies have shown that the neuron-specific- enolase (NSE), S100B protein (S100B) and matrix metalloproteinase-9 (MMP9) are specific markers for studying cerebral injury. This study was aimed to demonstrate these biomarkers for their correlation with reperfusion after carotid artery stenting (CAS). In this study, a total of 44 patients who were diagnosed unilateral carotid artery stenosis by digital subtraction angiography (DSA) and underwent CAS, were selected as the operation groups. The patients' blood samples were collected at three different time points: T1, prior to operation; T2, next morning after operation (24 hours); T3, three days after operation (72 hours); All of the patients with the operation received computed tomography perfusion (CTP) at T1 and T3. The second group of 12 patients, who were excluded for carotid artery stenosis by DSA, were assigned to be the control group; Blood samples of these patients were collected at T1. The concentrations of NSE, S100B and MMP9 in serum from patients of both groups were detected by ELISA. All of the operations were implanted in stents successfully without complications. (1) After CAS, rCBF increased while rMTT and rTTP decreased. (2) The concentrations of NSE, S100B and MMP9 in the serum decreased gradually (T1>T2>T3). There was no significant difference between the control group and the operation group at T1 (P>0.05) on their concentrations of NSE, S100B and MMP9 in the serum. When compared among the operation groups, the concentrations of NSE, S100B and MMP9 in the serum at T1 and T3 showed significant difference (P<0.05). (3) Correlation analysis among the operation groups indicated that NSE, S100B, MMP9 and rCBF were positively correlated before operation (r = 0.69, 0.58 and 0.72, respectively, P < 0.05), as well as after operation (r = 0.75, 0.65 and 0.60, respectively, P < 0.05). We concluded that the concentrations of NSE, S100B and MMP9 in serum decreased with the improvement of cerebral reperfusion after CAS. NSE, S100B and MMP9 can be used as laboratory biochemical markers to evaluate the improvement of reperfusion after CAS. The results very well complement the imaging methods, such as CTP.

Hypertension, matrix metalloproteinases and target organ damage.

Basal catalase activity and high glutathione levels influence the performance of non-Saccharomyces active dry wine yeasts

Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear. We performed a genome-wide association study of serum MMP-8 levels in 2 populations comprising altogether 6049 individuals. Moreover, we studied whether MMP-8-associated variants are linked to increased risk of CVDs and overall mortality in >20 000 subjects. The strongest association with serum MMP-8 was found in locus 1q31.3, containing the gene for complement factor H (lead single nucleotide polymorphism: rs800292; P=2.4×10-35). In functional experiments, activation of the alternative pathway of complement in the carriers of rs800292 minor allele (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared with the major allele (Val62 in factor H). Another association was detected in 1q21.3, containing genes S100A8, S100A9, and S100A12 (strongest association: rs1560833; P=5.3×10-15). The minor allele of rs1560833 was inversely associated with CVD (odds ratio [95% confidence interval]: 0.90 [0.82-0.99]; P=0.032) and the time to incident CVD event (hazard ratio [95% confidence interval]: 0.91 [0.84-0.99]; P=0.032) in men but not in women. According to our results, the activation of the alternative pathway of the complement system strongly contributes to serum MMP-8 concentration. Genetic polymorphism in S100A9-S100A12-S100A8 locus affects serum and plasma MMP-8 and shows a suggestive association with the risk of CVDs. Our results show that genetic variation determines a significant portion of circulating MMP-8 concentrations.

Objective: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor that is highly prevalent in Southeast Asia. The two traditional NPC markers VCA-IgA (EBV viral capsid antigen) and EA-IgA (EBV early antigen) are limited in the screening and diagnosis of NPC. The purpose of present study is to evaluate the diagnostic value of matrix metalloproteinase-3 (MMP3) in NPC.Methods: The levels of 23 secretory MMPs in serum samples from 15 healthy controls and 26 NPC patients were detected by Cytokine Antibody Array 2000. Immunohistochemistry, Real-time PCR and western bolt were used to detect MMP3 mRNA and protein levels in NPC tissues and cell lines. The serum protein levels of MMP3 were further measured by ELISA in healthy control individuals (n = 200) and NPC patients (n = 206).Results: MMP3 can be expressed and secreted by both NPC and fibroblast cell lines, suggesting that the higher expression of MMP3 protein in both tumor nests and stromal of NPC tissues may be the source of circulating MMP3 in NPC patients. Furthermore, we found out both MMP3 concentration and enzymatic activity were significantly increased in the NPC group (n = 206) than the healthy control group (n = 200) (P < 0.001). However, serum MMP3 enzymatic activity, but not MMP3 concentration, was significantly associated with the progression of NPC. In addition, serum MMP3 activity was more valuable in diagnosis of NPC than its concentration (0.86 vs. 0.78, AUC), and MMP3 activity can improve the diagnosis of NPC by combining with EBV-infection biomarkers VCA-IgA and EA-IgA with a sensitivity of 91.5% and a specificity of 92.3%.Conclusions: This study suggested the combination of MMP3 activity and EBV antibodies may be a useful biomarker for screening and diagnosis of NPC.

We investigated whether luteolin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as production of MMP-3 in the rat knee to evaluate the potential chondro-protective effects of luteolin. Rabbit articular chondrocytes were cultured in a monolayer and IL-1β-induced gene expression levels of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen were measured by reverse transcription - polymerase chain reaction (RT-PCR). Effects of luteolin on interleukin-1β (IL-1β)-induced secretion and enzyme activity of MMP-3 in rabbit articular chondrocytes were investigated by western blot analysis and casein zymography, respectively. The effect of luteolin on MMP-3 protein production was also examined in vivo. The results were as follows: (1) luteolin inhibited the gene expression levels of MMP-3, MMP-1, MMP-13, ADAMTS-4 and ADAMTS-5. However, it increased the gene expression level of collagen in rabbit articular chondrocytes; (2) luteolin inhibited the secretion and activity of MMP-3; (3) luteolin inhibited in vivo production of MMP-3 protein. These results suggest that luteolin can regulate the gene expression, secretion and activity of MMP-3, by directly acting on articular chondrocytes.

This study was conducted to compare the effect of active dry yeasts (ADY) and yeast cultures (YC), two typical products of yeast preparations, on growth performance, carcass characteristics, meat quality and blood indexes in finishing bulls fed a high-concentrate diet. Forty-five finishing bulls (mean body weight (BW) ± standard deviation: 505 ± 29 kg BW) were allocated to three groups of 15 bulls and assigned randomly to one of three diets which were CON diet (basal diet), ADY diet (basal diet + Levucell SC) and YC diet (basal diet + Diamond V XP), respectively. After 98 days of trial, all bulls were slaughtered. The result showed that ADY rather than YC improved growth performance and carcass traits of bulls compared to CON. Moreover, both ADY and YC improved beef tenderness and changed blood indexes related to fat metabolism. In conclusion, ADY had more pronounced effect on growth performance of bulls fed high-concentrate diet, and both ADY and YC improved the beef quality by intensive fat metabolism.

The significance of serum active matrix metalloproteinase-9 in patients with non-small cell lung cancer

Background and AimsMetalloproteinases (MMPs) are involved in many distinct processes in the liver. Matrix metalloproteinase-3 (MMP-3) plays an important role in connective tissue remodeling, degradation of collagen (types II, III, IV, IX, and X), proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease, characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. Fibrosis is the result of an imbalance between production and degradation of the extracellular matrix surrounding hepatocytes. Our aim in the present study was to determine whether the measurement of serum MMP-3 is clinically useful for assessing ongoing liver fibrosis in patients with PBC.MethodsThe MMP-3 concentration was determined in 182 PBC patients and 80 non-PBC controls using a commercially available ELISA kit.ResultsHigher concentrations of MMP-3 were found in 61% of PBC patients. PBC subjects had greater MMP-3 levels than controls: 68.9 ± 62.6 vs 21.3 ± 7.4 ng/mL, p < 0.001 for healthy subjects; 68.9 ± 62.6 vs 22.7 ± 7.6 ng/mL, p = 0.022 for autoimmune hepatitis controls; and 68.9 ± 62.6 vs 37.2 ± 17.4 ng/mL, p = 0.002 for primary sclerosing cholangitis controls. The serum MMP-3 concentration was significantly elevated in patients with higher bilirubin concentration (107.6 ± 85.8 vs 61.6 ± 46.1 ng/mL, p < 0.001) and was correlated with the level of antimitochondrial antibodies specific for PBC. The concentration of MMP-3 in sera of PBC patients was also found to correlate with the state of liver fibrosis (OR = 4.3; p < 0.01).ConclusionsOur study demonstrated significantly higher MMP-3 levels in PBC patients than in healthy and pathological controls. Increased MMP-3 concentrations were positively correlated with various clinical and immunological parameters, and advanced liver fibrosis. The level of MMP-3 was associated with hepatic dysfunction and could play a role in the pathophysiology of hepatic fibrosis in PBC.

The invasion and metastases of gastric cancer (GC) depends on the activities of matrix metalloproteinases and tissue inhibitors of metalloproteinases. It was suggested that the concentration of plasma matrix metalloproteinase-9 (MMP-9) is better than the concentration of serum MMP-9 for prediction of evolution of GC. The aim of the present study was to compare the clinical usefulness of plasma and serum tissue inhibitor of metalloproteinases-1 (TIMP-1) in the diagnosis and prognosis of GC. Plasma and serum concentrations of TIMP-1, MMP-9 and carcinoembryonic antigen (CEA) were assayed in 73 patients with GC and 61 healthy controls. The diagnostic criteria and prognostic value for the measurands were defined. Plasma and serum TIMP-1, MMP-9 and CEA were significantly higher in GC patients compared with healthy controls. The area under the ROC curve (AUC) (0.961), diagnostic sensitivity (89%) and accuracy (91%) of plasma TIMP-1 were higher than those for MMP-9 and CEA. An increased pre-treatment concentration of plasma TIMP-1 was a significant independent prognostic factor for the survival of patients with GC. These findings suggest that the plasma TIMP-1 is a better biomarker than the serum TIMP-1 and might be useful for the diagnosis of GC and prognosis of patient survival.