Plasma Alkaline Phosphatase Levels Research Articles

Risk factors for peripheral artery disease and diabetic peripheral neuropathy among patients with type 2 diabetes

AimsTo investigate the prevalence of peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) and the associated risk factors among Chinese patients with type 2 diabetes mellitus. MethodsA cross-sectional study was conducted using data between November 1, 2018, and December 31, 2022. PAD was defined as ABI ≤ 0.9. DPN diagnosis involved specialized physician assessments using questionnaires and vibration perception threshold tests. Logistic regression analysis was used to identify related factors. We also evaluated the association between the clustering of risk factors and disease incidence. ResultsThe study population comprised 13,315 patients (mean age: 63.3 years). 4.9 % of the patients had PAD and 43.9 % had DPN. Multivariate regression analysis revealed advanced age, smoking, hypertension, coronary heart disease, dyslipidemia, elevated HbA1c, and uric acid levels as independent risk factors for PAD. For DPN, independent risk factors included advanced age, female gender, hypertension, coronary heart disease, elevated total cholesterol, triglycerides, lipoprotein(a), fasting plasma glucose, HbA1c, alkaline phosphatase, cystatin C, albumin-to-creatinine ratio, and elevated homocysteine levels, whereas apolipoprotein A was a protective factor. The clustering of risk factors was prevalent and associated with higher disease risk. ConclusionsOur study contributed to identifying high-risk individuals and improving lower limb health among diabetic individuals.

Alkaline phosphatase and mortality in stroke patients: a systematic review.

Increased plasma levels of alkaline phosphatase (ALP) have been associated to a worse prognosis in several types of diseases. In the present review, the authors aimed to study the relationship between plasma levels of ALP and overall mortality in patients with stroke. A systematic review was carried out, searching two databases: Web of Science and Medline/PubMed. A total of nine studies that included data on overall mortality in stroke patients were selected. The selected studies were published between 2010 and 2022 and were predominantly from Asia. The articles reviewed quantified ALP levels through different methods: highest versus lowest quintiles of plasma ALP (three reports); highest versus lowest quartiles of plasma ALP (four reports); and plasma ALP levels in deceased versus in surviving patients (two reports). All selected studies showed an increased mortality associated to elevated ALP levels, irrespective of stroke type and length of follow-up, from a mean of 10 days to 2.5 years. The studies comparing the highest to the lowest ALP quintiles showed an aggregate value of 1.8 times greater risk of mortality for the former, when compared to the latter. Whereas, the studies comparing the highest to the lowest ALP quartiles showed an aggregate value of 2.4 times greater risk of mortality for the former, when compared to the latter. Elevated ALP levels are associated with increased mortality in stroke patients and provide cost effective prognostic indicators of mortality in stroke.

Effects of testosterone replacement on lipid profile, hepatotoxicity, oxidative stress, and cognitive performance in castrated wistar rats.

Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.

Health status, antioxidants and milk quality of goats reared under stall-fed and free range grazing system

The present study was conducted to determine health status and milk quality of goats reared under stall fed and free range grazing system. The research areas reported higher THI throughout the summer. Respiration rate (RR) and heart rate (HR) was significantly higher during summer in both the groups. Both groups had significantly increased neutrophils and eosinophils during the summer and increased Hb, PCV, and lymphocyte during the winter. Stall fed goats had significantly higher MDA during summer. The free range group had significantly higher levels of SOD and GSH in the summer and winter, respectively.Vitamins C and E levels declined during the summer. In both the groups, summer levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and plasma alkaline phosphatase (ALP) were significantly higher but remained within the reference range. During the summer, both groups of goats showed a significant decrease in plasma glucose, triglycerides, and cholesterol. Total proteins (TP) and Albumin both significantly declined during the winter in both the groups. Total immunoglobulins significantly increased during the winter in the free range group. Throughout the winter and the summer, respectively, the fat percentage increased in the milk of the stall-fed and free-range groups. Moreover, solid not fat (SNF) significantly declined in stall fed group during the winter. Also, there was no discernible difference in the amount of milk proteins between the groups; however, during the summer, it was discovered that stall-fed goats had more of them. The milk lactose significantly increased in both the groups in the time of summer though the increase was remarkable in stall fed goats. The present study indicated that stall fed and free range reared goats in winter and summer exhibit physiological variation in their health state, milk production, and composition.

Effects of humic acid on nutrient removal efficiency of aquatic duckweed (Lemna minor) and both growth performance, and hemato-biochemical parameters of Nile tilapia (Oreochromis niloticus) cultured in water recirculating system

This study was carried out to evaluate the effects of humic acid (HA) on the nutrient removal efficiencies of aquatic duckweed plant (Lemna minor) from a water recirculating system used to culture Nile tilapia (Oreochromis niloticus) fish for 30 days. The HA was added to water at three concentrations of 0 (Control), 1.5, and 3 mg/L in triplicate. Water quality parameters, growth performance, and some hemato-biochemical parameters of the fish in variable HA concentrations were compared. The total ammonia nitrogen (TAN) and total phosphorous (TP) removal efficiency of L. minor increased with increasing the HA concentration from 0 mg/L to 3 mg/L (p < 0.05). The concentration of nitrate (NO3 −) in the HA-3 mg/L was higher than that in the other groups on days 20 and 30 of the fish cultivation period (p < 0.05). The growth performance of fish improved in the HA-3 mg/L compared to the other groups. The addition of different concentrations of HA to water had no adverse effect on the hematological properties of the Nile tilapia. The plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in the HA-0 mg/L and HA-1.5 mg/L groups were higher than in the HA-3 mg/L (p < 0.05). No significant differences in the plasma glucose and cholesterol levels were observed between the HA-groups (p > 0.05), while the triglyceride level increased in the HA-3 mg/L compared to the control (p < 0.05). These results indicated that adding HA to water could be an effective method to enhance the bioremediation performance of the aquatic duckweed plants as biofilter and thus improve water quality, subsequently, fish growth performance in RASs.

Transcriptomic analysis reveals the molecular mechanisms underlying osteoclast differentiation in the estrogen-deficient pullets

Several previous reports have suggested that estrogen (E2) is a vital signal responsible for the regulation of skeletal homeostasis and bone remodeling in mammals. E2 could efficiently accelerate the growth of medullary bone in pullets during sexual maturity. Furthermore, the low E2 level can strengthen the mechanical bone functions in female hens. However, mechanistic studies to describe the effects of E2 on bone in pullets during the initiation of the puberty period are remaining elusive. Therefore, the aim of this study was to explore the effect of inhibiting E2 biosynthesis on the biomechanical properties and its molecular mechanism during sexual maturity of pullets. In this study, a total of 90 Hy-line Sonia pullets with comparable body weight at 13 wk of age were selected and categorized into 2 separate groups. Daily, 0.5 mg/4 mL of letrozole (LZ) was orally administered to the treatment (TRT) group and 4 mL of saline to the control (CON) group of pullets for 6 wk. Compared with the CON group, a lower plasma E2 level was observed in the TRT group. Furthermore, plasma P, Gla protein (BGP), and 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) levels were markedly suppressed, whereas the plasma alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels were significantly elevated. Moreover, the cortical bone thickness and breaking strength of the tibia and femur, the bone mineral density of the humerus, and the bone mineral content of the humerus as well as the femur were increased significantly. The expression levels of 340 differentially expressed genes (DEGs) differed significantly between the CON and TRT group in the tibia at 19 wk of age. Among them, 32 genes were up-regulated, whereas 308 were down-regulated in the TRT group. The variations in candidate genes associated with osteoclast differentiation and cell adhesion may indicate that LZ inhibits E2 biosynthesis, consequently, reduces osteoclast differentiation by suppressing inter-cellular communication and cells attaching to extracellular matrix components. Taken together, the present study demonstrated that inhibiting E2 synthesis during sexual maturity of pullets decreased osteoclast differentiation and considerably enhanced bone quality.

Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults.

We investigated the utility of urine phosphoethanolamine (PEA) as a marker to aid in diagnosing and/or confirming hypophosphatasia (HPP) in adults and for monitoring patients on enzyme replacement therapy (ERT). Data was collected from seventy-eight adults who were referred to the Vanderbilt Program for Metabolic Bone Disease for evaluation of a possible or confirmatory HPP diagnosis between July 2014 through December 2019. Fifty-nine patients were diagnosed with HPP and nineteen were excluded from a diagnosis of HPP. The urine PEA results of those patients with a confirmed diagnosis of HPP and those patients with a diagnosis of HPP excluded were captured and compared to other laboratory and clinical parameters consistent with HPP, including alkaline phosphatase (ALP) activity, plasma pyridoxal 5'-phosphate (PLP), the presence of musculoskeletal abnormalities, and genetic testing for pathogenic mutations in ALPL. Initial urine PEA values in patients in our HPP cohort and not on ERT were significantly higher (median=150.0nmol/mg creatinine, IQR=82.0-202.0) compared patients in our HPP negative group (median 18.0nmol/mg creatinine, IQR=14.0-30.0, p<0.0001) and higher than patients on ERT (median 65.0nmol/mg creatinine, IQR=45.3-79.8). Patients who began ERT had a decline in urine PEA levels after treatment with a mean decrease of 68.1%. Plasma ALP levels were significantly lower in the group of patients with HPP and not on ERT group (median=24.0U/L, IQR=15.0-29.50) compared to the patients without HPP (median=45.50U/L, IQR=34.0-62.0;) and plasma PLP levels were significantly higher in the HPP non-ERT group (median=284.0nmol/L, IQR=141.0-469.4) compared to the patients without HPP (median=97.5nmol/L, IQR=43.7-206.0;). The area under the curve (AUC) of urine PEA, ALP, and PLP to distinguish between HPP and non-HPP patients is 0.968, 0.927 and 0.781, respectively, in our cohort. Urine PEA had 100% specificity (95% CI of 83.2% to 100.0%) for diagnosing HPP at a value >53.50nmol/mg creatinine with a sensitivity of 88.4%; 95%CI 75.5 to 94.9%. ALP had a 100% specificity (95% CI of 82.4% to 100.0%) for diagnosing HPP at a value <30.5U/L with a sensitivity of 77.2%; (95%CI 64.8 to 86.2%). PLP had a 100% specificity (95% CI of 81.6% to 100.0%) for diagnosing HPP at a value >436nmol/L with a sensitivity of 26.9%; (95%CI 16.8 to 40.3%). The most common pathogenic or likely pathogenic mutations in our cohort were c.1250A>G (p.Asn417Ser), c.1133A>T (p.Asp378Val), c.881A>C (p.Asp294Ala), c.1171C>T (p.Arg391Cys), and c.571G>A, (p.Glu191Lys). Urine PEA is a promising diagnostic and confirmatory marker for HPP in patients undergoing investigation for HPP. Urine PEA also has potential use as a marker to monitor ERT compliance. Future studies are necessary to evaluate the association between PEA levels and clinical outcomes.

Plasma alkaline phosphatase is associated with mortality risk in patients with aortic valve stenosis.

Background: Aortic valve stenosis is an important clinical condition, with a significant mortality rate in the elderly. Plasma values of alkaline phosphatase (ALP) have been shown to act as a marker of prognosis in different clinical conditions and in the general population. Methods: Plasma levels of ALP were studied in a cohort of patients with aortic valve stenosis, and a 5-year survival evaluation was performed. Results: Twenty-four patients were under study, of whom 12 were dead at the 5-year follow-up. The median age at baseline evaluation was 79 years (interquartile range, 72-85 years), and 11 patients were female (13 were male). The median value of ALP, of 83 IU/L, was used to separate patients into two groups: 2 patients who died in the group with low ALP values versus 10 patients who died in the group with high ALP values. Using ALP with the same cutoff level, the Kaplan-Meier study with log-rank analysis showed a significance level <0.01. Cox regression analysis showed an overall significant result, with a significant level for plasma ALP (significance level 0.03), but not for age, sex, or transvalvular gradient (assessed by echocardiography). Conclusions: Elevated plasma ALP is associated with increased mortality risk in patients with aortic valve stenosis. This finding may merit evaluation in studies with a larger number of patients.

Protective effects of paeonol against lipopolysaccharide-induced liver oxidative stress and inflammation in gibel carp (Carassius auratus gibelio)

Paeonol (2′-hydroxy-4′-methoxyacetophenone) is a phenol that exhibits antioxidant and anti-inflammatory capabilities. In this study, the underlying mechanism of paeonol against LPS-induced oxidative stress and inflammatory responses in gibel carp was investigated. Three hundred healthy gibel carp were divided into five groups (n = 9), intraperitoneally injected with LPS and thereafter treated with paeonol (16 mg/kg and 64 mg/kg). Fish were anesthetized with MS-222 (100 mg/L), and samples were collected at 72 h to investigate plasma biochemical indexes, liver histopathology, antioxidant enzymatic activity, and TLR receptor-related gene expression. Fish injected with LPS (20 mg/kg) exhibited significantly increased plasma aminotransferase (ALT), aminotransferase (AST), lactate dehydrogenase (LDH), glucose (GLU), diamine oxidase (DAO), and alkaline phosphatase (ALP) levels (P < 0.05). In addition, LPS challenge significantly enhanced myeloperoxidase (MPO) and malondialdehyde (MDA) contents, whereas those of catalase (CAT) and glutathione peroxidase (GSH-Px) decreased (P < 0.05). However, treatment with paeonol attenuated these LPS-induced changes (P < 0.05). The mRNA expression of TLR4, TIRAP, MyD88, TRAF6, NF-κB, TNF-α, IL-1β, and IL-8, which were activated by LPS challenge (P < 0.05), were downregulated by paeonol. Additionally, histopathological examination demonstrated that paeonol alleviates LPS-induced hepatic tissue lesions in fish. Taken together, the results suggest that paeonol mitigates LPS-induced liver oxidative stress and inflammation in gibel carp.

A Retrospective Case-Control Study on Late Failure of Arteriovenous Fistula in Hemodialysis Patients and Prediction of Risk Factors.

Objective A retrospective case-control study was conducted to explore the risk factors of late failure of arteriovenous fistula in hemodialysis patients. Methods A total of 95 hemodialysis patients treated in our hospital from January 2018 to January 2021 were included. The HE staining results of late failure of arteriovenous fistula in hemodialysis patients were observed. The general data and laboratory indexes of the patients were recorded by using a questionnaire survey, hospital case system, and hemodialysis record. According to the functional status of internal fistula, the patients were divided into two groups: failure group (n = 35) and patency group (n = 60). SPSS22.0 software was employed for statistical analysis, and the relevant data of the two groups were compared. The independent sample t-test was employed for the comparison of variance between groups, and the χ2 test was employed for counting data. Logistic multivariate regression was employed to analyze the risk factors of late loss of power in autologous arteriovenous fistula (AVF). Results (1) Late failure of arteriovenous fistula in hemodialysis patients: the results of HE staining showed the following: (1) histological changes of venous intima: 100% of the patients had varying degrees of intimal hyperplasia, mainly eccentric hyperplasia, resulting in luminal stenosis, and annular uniform intimal hyperplasia in some patients, and (2) histological changes of venous media: 81.6% of the patients had venous media lesions, which were mainly in two cases; one was media smooth muscle hyperplasia with fibrous tissue hyperplasia, and the other was smooth muscle compression when intimal hyperplasia was serious, resulting in smooth muscle fiber rupture, disarrangement, focal necrosis, atrophy, and thinning, and some smooth muscle stroma showed vitreous degeneration and myxoid degeneration. A few cases showed multifocal neutrophil, lymphocyte, and plasma cell infiltration. (2) First of all, we surveyed the general data, and there were significant differences in age, history of diabetes, history of hypertension, and uric acid nephropathy (P < 0.05). There was no significant difference in sex, body mass index, smoking history, polycystic kidney disease, chronic glomerulonephritis, and obstructive nephropathy between the two groups (P > 0.05). Secondly, we compared the levels of hemoglobin, eosinophils, platelet count, and hematocrit. The levels of hemoglobin, eosinophils, and hematocrit in the failure group were higher, and the platelet count was lower compared to that of the unobstructed group (P < 0.05). Furthermore, the calcium and phosphorus product and the level of C-reactive protein (CRP) in the failure group were higher, while the levels of fibrinogen and INR in the unobstructed group were lower. The levels of plasma protein, alkaline phosphatase, and cholesterol were higher in the failure group, while the level of triglyceride was lower in the failure group (P < 0.05). Finally, logistic regression analysis showed that age, hemoglobin, hematocrit, and calcium-phosphorus product were the risk factors for late failure of arteriovenous fistula in hemodialysis patients (P < 0.05). There exhibited no significant correlation between diabetes, hypertension, uric acid nephropathy, eosinophil, CRP, fibrinogen, INR, plasma protein, alkaline phosphatase, cholesterol, triglyceride, and late failure of arteriovenous fistula in hemodialysis patients. Conclusion Age, hemoglobin, hematocrit, and calcium-phosphorus product are independent risk factors for late failure of arteriovenous fistula in hemodialysis patients. The hemoglobin, eosinophil, platelet count, and hematocele in hemodialysis patients with late failure of arteriovenous fistula were higher. The indexes related to biochemistry, blood coagulation, and nutrition were significantly different from those without late failure of arteriovenous fistula. Thus, the risk of late failure of arteriovenous fistula can be predicted.

The Allium triquetrum L. Leaves Mitigated Hepatotoxicity and Nephrotoxicity Induced by Lead Acetate in Wistar Rats.

The aim of this study was to scrutinize the possible mitigating role of leaves' Allium triquetrum L. against the toxicity of lead acetate on liver and kidney markers of Wistar rat. Lead acetate (Pb) and leaves' aqueous extracts (L) were orally administrated for 3 weeks. Rats were divided into the control, Pb group (500 mg/kg body weight/day), positive controls L (2g, 3g, 4g/kg BW/day), along with three combined groups of the same doses (Pb-L1, Pb-L2, Pb-L3). The levels of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins (TP), albumin (ALB), urea, creatinine (Cr), and uric acid (UA), as well as the hepatic and the renal malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx), were estimated. Results exhibited a significant increase in plasma AST, ALT, ALP, urea, creatinine, uric acid, and MDA levels of the Pb group compared to the control, with the exception of TP, ALB, GSH levels, and GPx activities that were significantly diminished, though the co-administration of garlic extracts (Pb-L) revealed a significant decrease in all mentioned markers, excluding the TP, ALB, GSH, and GPx levels. Likewise, Pb caused histological injuries in the hepatic and renal tissues of rats, while the co-administration of leaves' wild garlic has reduced such effect. Thought, the Pb-L has attenuated the Pb-induced toxicity in a dose-dependent manner. In conclusion, the aqueous extracts of A. triquetrum have the potential to alleviate Pb hepatotoxicity and nephrotoxicity through the modulation of most biomarkers in Wistar rat.

Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats.

Simple SummaryModern intensive production methods attract accusations of poor animal welfare due to long-term exposure to stressors including high temperature, persistent humidity and overcrowding. Stress can be defined as any condition that threatens the physiological homoeostasis and hypothalamic-pituitary-adrenal (HPA) axis responses that tend to restore the prior stable status of the organism. Uncontrollable and unpredictable sources of stress can cause various forms of damage to the liver, which is the central mediator of systemic iron balance. Iron, notably, is an essential element for maintaining health in virtually all organisms. We found that chronic variable stress can cause weight loss and disorders of the liver iron metabolism in rats, thereby triggering liver oxidative damage. Our results also suggest that the miR-181 family is a potential target for treating iron overload-associated diseases.It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.

Gill oxidative damage caused by acute ammonia stress was reduced through the HIF-1α/NF-κb signaling pathway in golden pompano (Trachinotus ovatus)

This study aimed to investigate the intoxication mechanism of golden pompano (Trachinotus ovatus) exposed to high ammonia levels and the effects on the immune and antioxidant mechanisms of gills. Juvenile golden pompano was exposed to ammonia (total ammonia: 26.9 mg/L) to induce 96 h of ammonia stress, and a 96 h recovery experiment was performed after poisoning. Then, we evaluated hematological parameters, the histological structure and the expression of related genes. In this experiment, continuous exposure to high levels of ammonia led to a significant increase in plasma alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels (P < 0.05), and the levels of triiodothyronine (T3) and tetraiodothyronine (T4) were significantly reduced (P < 0.05). Moreover, the expression of antioxidant genes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) increased (P < 0.05). These results indicate that ammonia activates the active osmotic regulatory mechanism of fish gills and participates in defense and immune responses. However, with prolonged exposure to ammonia, the balance of the defense system is disrupted, leading to oxidative damage and inflammation of the gill tissue. This research not only helps elucidate the intoxication mechanism of golden pompano by ammonia at the molecular level but also provides a theoretical basis for further research on detoxification mechanisms.

The effects of long-term thyroxine administration on hematological, biochemical and immunological features in sterlet sturgeon (Acipenser ruthenus)

This study examined the effects of thyroxine (T4) on hematological indices, immune parameters and the stress markers of female sterlet sturgeon. Adult broodstock (708 ± 37 g) were assigned to three groups each consisting of ten females. Fish were injected with coconut oil (control), 1 mg T4 kg body weight−1 in coconut oil (T1) or 10 mg T4 kg body weight−1 in coconut oil (T10). Injections were given intraperitoneally four times over a 170-day treatment period. At the end of the experiment, hemato-biochemical and immunological changes were measured. Treatment with the high concentration of T4 led to a significant increase in weight gain at the end of the experiment. The number of red blood cells, hemoglobin content and hematocrit were also significantly higher in the T10 group compared to the other groups (P < 0.05). The lowest levels of plasma alkaline phosphatase, aspartate amino transaminase and lactate dehydrogenase were found in the T10 group (P < 0.05). Alanine amino transaminase did not differ between groups (P > 0.05). The highest levels of total protein, albumin, complement component 3, complement component 4, and immunoglobulin M were found in the T10 group (P < 0.05). Additionally, higher and lower levels of glucose were noted in T10 and T1 treatments, respectively. Cortisol concentration was highest and lowest in T10 and control groups, respectively (P < 0.05). These findings demonstrate the actions of T4 on multiple regulatory pathways controlling the physiological condition of sterlet sturgeon broodstock.

Effects of dietary zinc levels on growth performance, digestive enzyme activities, plasma physiological response, hepatic antioxidant responses and metallothionein gene expression in juvenile spotted sea bass ( Lateolabrax maculatus )

The current study was conducted to investigate the effects of dietary zinc on growth performance, body composition, feed utilization, digestive enzyme activities, plasma physiological response, antioxidant responses and metallothionein (MT) gene expression in juvenile spotted sea bass, Lateolabrax maculatus. Six experimental diets (D1-6) were formulated with increasing levels of Zn (0, 20, 40, 80, 160 and 320 mg/kg, respectively) supplied as ZnSO4·H2O. The concentrations of Zn in experimental diets were 36, 55, 74, 110, 175 and 327 mg/kg diet determined by analysis. Each experimental diet was assigned to triplicate groups of 25 L. maculatus for a period of 56 days. The weight gain (WG) and specific growth rate (SGR) in the D4, D5 and D6 groups were significantly increased than that of the control group (p < 0.05), while the feed conversion ratio (FCR) significantly decreased (p < 0.05), respectively. The zinc contents of plasma and vertebra were significantly affected by dietary zinc levels, with the highest zinc content of plasma and vertebra occurring in D6 group (p < 0.05). The levels of plasma alkaline phosphatase (AKP), glucose and catalase (CAT) in the D5 and D6 groups were significantly increased compared with those in the control group (p < 0.05). The content of aspartate aminotransferase (AST) and cortisol (COR) in the D3 and D4 groups was significantly decreased compared with that in the control group (p < 0.05). The intestinal Na+, K+-ATP and CK activities in D3 group were significantly higher than those in the control group (p < 0.05). Compared with the control, the D3 group significantly increased the activities of SOD and T-AOC (p < 0.05), and the D5 group significantly decreased the content of MDA (p < 0.05). The expression of intestinal metallothionein (MT) mRNA in D5 and D6 groups was significantly higher than that of fish in control, D2 and D3 groups (p < 0.05), respectively. Based on the broken-line regression analysis of SGR and AKP, the optimal dietary zinc levels for maximal growth of juvenile L. maculatus were estimated to be 92 and 107 mg/kg diet, respectively.

Chronic cholestasis detection by a novel tool: automated analysis of cytokeratin 7-stained liver specimens

BackgroundThe objective was to build a novel method for automated image analysis to locate and quantify the number of cytokeratin 7 (K7)-positive hepatocytes reflecting cholestasis by applying deep learning neural networks (AI model) in a cohort of 210 liver specimens. We aimed to study the correlation between the AI model’s results and disease progression. The cohort of liver biopsies which served as a model of chronic cholestatic liver disease comprised of patients diagnosed with primary sclerosing cholangitis (PSC).MethodsIn a cohort of patients with PSC identified from the PSC registry of the University Hospital of Helsinki, their K7-stained liver biopsy specimens were scored by a pathologist (human K7 score) and then digitally analyzed for K7-positive hepatocytes (K7%area). The digital analysis was by a K7-AI model created in an Aiforia Technologies cloud platform. For validation, values were human K7 score, stage of disease (Metavir and Nakunuma fibrosis score), and plasma liver enzymes indicating clinical cholestasis, all subjected to correlation analysis.ResultsThe K7-AI model results (K7%area) correlated with the human K7 score (0.896; p < 2.2e− 16). In addition, K7%area correlated with stage of PSC (Metavir 0.446; p < 1.849e− 10 and Nakanuma 0.424; p < 4.23e− 10) and with plasma alkaline phosphatase (P-ALP) levels (0.369, p < 5.749e− 5).ConclusionsThe accuracy of the AI-based analysis was comparable to that of the human K7 score. Automated quantitative image analysis correlated with stage of PSC and with P-ALP. Based on the results of the K7-AI model, we recommend K7 staining in the assessment of cholestasis by means of automated methods that provide fast (9.75 s/specimen) quantitative analysis.

Effect of anthocyanin extract from Roselle,Hibiscus sabdariffa, calyx on haematological, biochemical and immunological parameters of rainbow trout,Oncorhynchus mykiss

In the present study, rainbow trout, Oncorhynchus mykiss, (14.1 ± 0.08 g) were fed diets supplemented with different levels of Roselle anthocyanin extract (RE) to assess the fish immune, stress and haematological parameters. For this, four levels of RE including 0, 0.5, 1 and 1.5% were added to the fish diet for eight weeks. Then, growth performance, blood haematological, biochemical, immunological and hepatic expression of cytokine genes were investigated in all treatments. At the end of the experiment, the fish exhibited similar growth rate and survival (final weight: 91.4–96.7 g; feed conversion ratio: 0.75–0.80; specific growth rate: 3.11–3.21% d−1; survival: 100%). The results showed that there were no significant differences in plasma glucose, cholesterol, triglyceride, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase levels among the treatments. Supplementation of the diets with 1% RE significantly increased RBC, haemoglobin, haematocrit, lysozyme, complement and WBC, compared with the control treatment. 1 and 1.5% RE significantly decreased plasma cortisol levels, compared with the control. All levels of dietary RE significantly up-regulated hepatic tumour necrosis factor-alpha gene expression, compared with the control treatment. 1 and 1.5% RE significantly up-regulated hepatic interleukin-1 beta gene expression, compared with the control treatment. 1.5% RE supplementation significantly down-regulated interleukin-10 gene expression, compared with the other treatments. In conclusion, dietary RE supplementation at 1% is beneficial for rainbow trout, as it mitigates stress and increases immune-related parameters.

Bergenin Attenuates Sodium Selenite-Induced Hepatotoxicity via Improvement of Hepatic Oxidant-Antioxidant Balance in HepG2 Cells and ICR Mice

Bergenin is a C-glucoside derivative of gallic acid claimed to exhibit antioxidant and hepatoprotective activities. However, its effect on sodium selenite-induced oxidative damage has never been elucidated. We investigated the impact of bergenin on the oxidant-antioxidant balance in sodium selenite-induced oxidative stress in HepG2 cells and mouse livers. HepG2 cells were co-incubated with sodium selenite (10 μM) and either bergenin (75, 150, and 300 μM) or gallic acid (60 μM) for 24 h. Adult male ICR mice were orally administered sodium selenite (4 mg/kg/day) in combination with either bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 days. Sodium selenite injured HepG2 cells and mouse livers by disturbing the oxidant-antioxidant balance. Bergenin exerted protective effects against sodium selenite-induced oxidative stress in HepG2 cells. Moreover, bergenin attenuated sodium selenite-induced liver damage (nuclear pyknosis and necrotic areas) through a decrease in plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels, and decreased production of reactive oxygen species, resulting in reduced lipid peroxidation in plasma and livers. Bergenin also restored hepatic antioxidant enzyme expression levels and activities (superoxide dismutase, catalase, and glutathione peroxidase) and reinstated hepatic glutathione homeostasis. Finally, bergenin returned cytochrome P450 2E1 mRNA expression to normal levels. In conclusion, bergenin reduced-sodium selenite induced liver damage by restoring the oxidant-antioxidant balance and reducing lipid peroxidation through multiple pathways.

Expression Pattern of MicroRNA-21 during the Liver Ischemia/Reperfusion.

Ischemia/reperfusion (I/R) injury in cadaveric liver transplantation is not avoidable. Liver I/R injury is an important phenomenon in hepatic damage. MicroRNA-21 (miR-21) plays an important role in I/R injury. The present study aimed to determine the expression pattern of miR-21 in liver I/R injury/recovery and its correlation with the immunologic transmission signals pathways several days post-reperfusion. In an animal model for I/R in the liver, 40 male Balb/c mice were divided into 3 groups. The animals were monitored for 3 and 24 hours, and also for 4, 7, 14, and 28 days post-reperfusion. Liver tissue damage was assessed by histopathology. The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC) levels were measured with enzymatic assays. MiR-21, programmed cell death 4 (PDCD4) mRNA, T-cell-restricted intracellular antigen 1 (TIA1) mRNA, and fas ligand (FASL) mRNA expression levels were measured; using reverse transcription-polymerase chain reaction (RT-PCR) at different times after the reperfusion in liver tissue and blood. Histopathology and plasma ALT, AST, ALP, and TAC levels confirmed liver damage induced by I/R injury. MiR-21 increased by twofold in the liver tissue and on the inflammatory phase after 24 hours of reperfusion; it then continued to decrease up to day 7 post-reperfusion. Afterward, it continued to rise slightly up to day 14 post-reperfusion. This trend was in parallel with the recovery of the liver damage. MiR-21 expression level in the liver and blood is a predictor of the extent of I/R injury.

Premature Birth Infants Present Elevated Inflammatory Markers in the Meconium.

Introduction: Prematurity, a well-established risk factor for various intestinal diseases in newborns, results in increased morbidity and mortality. However, the intestinal inflammatory status of preterm (PT) infants has been poorly characterized. Here we have broadly described the intestinal and systemic inflammatory status of PT children.Materials and Methods: Meconium and plasma from 39 PT and 32 full term (T) newborns were studied. Fecal calprotectin, polymorphonuclear leukocyte elastase (PMN-E), TNF, IL-17A, IL-8, IP-10, MCP-1, MIP-1, IL-1β, IL-1α, and E-selectin and the enzymatic activities of myeloperoxidase (MPO) and alkaline phosphatase (AP) in meconium were measured. Plasma levels of AP, hepatocyte growth factor, nerve growth factor (NGF), proinflammatory cytokines, leptin, adiponectin, PAI-1, and resistin were also determined. Correlations with gestational age (GA) and birth weight (BW) were studied.Results: Neutrophil derived PMN-E, MPO and calprotectin were increased in the meconium of PT compared to T newborns, while AP was decreased. No significant differences were found in other inflammatory parameters. Considering data from all children, GA and BW showed inverse correlation with neutrophil markers, while AP directly correlated with BW. Plasma levels of IL-1β and NGF were enhanced in PT infants, and were also negatively correlated with BW. PT children additionally showed neutropenia and decreased adiponectin, leptin, haematocrit, and haemoglobin. These parameters (neutrophils, adiponectin, and so forth) were positively correlated with GA and BW, while IL-8, MCP-1, PAI-1, and plasma AP were negatively correlated. PT children showing postnatal morbidity exhibited increased meconium MPO and MIP-1α.Conclusion: PT neonates present a significant elevation of intestinal inflammatory parameters, characterized by the presence of neutrophil markers, associated with mild systemic inflammation.