Serum Biochemical Indices Research Articles

Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, Crat, Car3, and MNK-mediated apoptosis

Aluminum (Al) is a ubiquitous xenobiotic with known toxicity for both humans and animals. Our study was conducted to investigate the protective role of febuxostat (Feb) against aluminum chloride (AlCl3)-induced hepatorenal injury in rats. Hepatorenal injury was induced by oral administration of AlCl3 (40 mg/kg b.w.), for 2 months. Twenty-four male Sprague–Dawley rats were randomly allocated into four groups (six rats/group). The first group received the vehicle thought the experiment. The second group was considered as a control positive group. The third and fourth groups received oral treatment of Feb (10 mg/kg.b.w.) and (15 mg/kg.b.w.), respectively with AlCl3, concurrently for 2 months. Twenty-four hours, after the last treatment, serum biochemical, molecular, histopathology, and immunohistochemical studies were evaluated. Our findings showed that rats intoxicated with Alcl3 had disturbed biochemical picture. In addition, intoxication with AlCl3 increased oxidative stress and apoptosis, as demonstrated by an increase in malodialdeyde (MDA), carnitine o-acetyltransferase (Crat), and carbonic anhydrase (Car3) with a decrease in glutathione (GSH), MAP kinase-interacting serine/threonine kinase (MNK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) mRNA expression. Furthermore, the levels of tumor necrosis factor-alpha (TNF-α) and the levels of caspase-3 were elevated with sever hepatic and renal pathological changes. Conversely, Feb (15 mg/kg.b.w.) could improve the serum biochemical indices and repressed MDA, Crat, and Car3 levels, whereas it increased GSH, MNK, and Nrf2 levels. Feb inhibited the apoptotic effect of AlCl3 in the liver and kidney by decreasing caspase-3 and TNF-α expression. The protective effect of Feb against AlCl3 toxicity was confirmed by histopathological findings. Moreover, molecular docking studies supported the anti-inflammatory effect of Feb due to its significant binding interactions with cyclooxygenase-1 (COX-1), NF-kappa-B-inducing kinase (NIK), and mitogen-activated protein kinases-p38 (MAPK-p38). The findings suggest that Feb system Feb can avert Alcl3-induced hepatotoxicity and nephrotoxicity by enhancing the antioxidant defense system, and inhibiting the inflammatory cascade and apoptosis.

Haematological and serum biochemical indices of cocks drenched varying levels of clove powder (Syzygium aromaticum)

There is stimulated increased interest in the usage of consumer accepted natural alternatives such as phytogenic feed additive (PFAs) to improve livestock performance. Clove is a wonderful phytogenic feed additives with little information in its benefit in poultry production. This study was conducted to assess the effect of clove powder (Syzygium aromaticum) on haematological and serum - biochemical indices of cocks. Clove was obtained from a local market in Saki, Oyo State. Dried clove buds were cleaned and air dried for 24 hours prior to milling and stored in air-tight bags until the period of usage. Cocks (48 birds assigned into four treatments) were drenched at 0.0g (T1), 0.05g (T2), 1.00g (T3) and 1.5g (T4) after 2 weeks of acclimatization. Haematological parameters measured were: packed cell volume (PCV), red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb), mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). While biochemical evaluated were total protein, albumin, globulin, uric acid, creatinine, cholesterol and glucose. Data obtained were subjected to one-way analysis of variance in a completely randomised design. RBC (3.64 – 3.76 X106/mL), Hb (3.64 – 12.86 g/dL), MCH (32.79 – 36.86 μμg) and MCHC (31.62 – 32.85%) showed significant difference (P<0.05), while PCV (39.00 – 41.00%), WBC (18.66 – 19.10 X109/mL), MCV (103.74 – 112.23 μ3) shows no significant difference (p>0.05). Total protein showed significant difference (P<0.05) with values ranging between 4.46 and 5.40 g/dL There exists significant difference (P<0.05) in the mean value of albumin, with highest value in 1.50g CP (5.40). Other biochemical parameters studied also showed significant differences (P<0.05) with the highest value in 1.50g CP. Drenching cocks with clove powder up to 1.5g was discovered posing no harmful effect on cocks.

Effect of oligonucleotide MT01 delivered by N-isopropylacrylamide modified polyethyleneimine for bone regeneration.

Objective: This study aimed to investigate the regulatory effect of N-isopropylacrylamide-modified polyethyleneimine (PEN)-delivered oligodeoxynucleotide (ODN) MT01 on bone regeneration in vitro and in vivo. Methods: A polyethylenimine (PEI) derivative, PEN, was constructed through Michael addition and employed as a carrier for ODN MT01 transfection. PEN/MT01 nanocomposites were characterized using agarose gel retardation assay, size distribution, zeta potential and transmission electron microscopy. The Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of PEN on cell viability. Alkaline phosphatase (ALP) staining was used to detect the osteogenic differentiation ability of PEN/MT01 nanocomposite. Real-time quantitative PCR (q RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulatory effects of PEN/MT01 nanocomposite on osteogenic differentiation gene expression. Rat model was observed using the skull defect method and verified using micro-computed tomography (CT), serum biochemical indices, hematoxylin and eosin (H&E) staining and Immunohistochemistry (IHC). Results: PEN had good biological properties and could deliver MT01 well to achieve efficient transmission of MT01. PEN/MT01 nanocomposites were effectively transfected into MC3T3-E1 cells at a ratio of 6.0. CCK-8 assay displayed that PEN had no cytotoxicity to MC3T3-E1 cells. Additionally, PEN/MT01 nanocomposites could promote the expression of osteogenic genes. In vivo results revealed that PEN/MT01 nanocomposites could promote bone regeneration more effectively than the other groups. Conclusion: PEN has good biocompatibility and low toxicity, which is a good carrier for ODN MT01. PEN-delivered MT01 can be potentially employed as a useful approach to achieving bone regeneration.

Spirulina Platensis Protective Effects Against Acute Fenitrothion - Induced Toxicity in Rats

The aim of the study is to Spirulina protective effects against acute Fenitrothion-induced toxicity in rats. The objective of a present investigation has been to determine if Spirulina could protect male Wistar albino rats from the toxic effects of Fenitrothion by acting as an antioxidant and hepato-nephroprotector. The toxic effects of DLM are significantly influenced by oxidative stress. In numerous earlier interventions, antioxidants are useful in reducing DLM-induced toxicity. Spirulina is a strong antioxidant that has the potential to lessen the effects of numerous common chemotherapeutic drugs and insecticides. It is evident from the current study that DLM exposure caused variable changes in serum biochemical indicators, levels of lipid peroxidation, and the inhibition of antioxidant enzyme activity. In terms of biochemical changes in blood and tissues, antioxidant enzyme activity, and oxidative stress, AP pre-exposure offered almost full protection.

Effects of Dietary Supplementation of Vitex doniana (Black Plum) Leaf Meal on Growth Performance, Blood Parameters, Carcass Traits, and Relative Organ Weights of Broiler Chickens

Introduction: Evaluation of using plants, such as Vitex doniana leaf meal as an alternative feed resource in broiler diets decreases the feed costs. The current study examined how air-dried Vitex doniana, Black Plum Leaf Meal (BPLM) could affect broiler chicken growth performance, hematological parameters and serum biochemical indices, carcass yield, and relative organ weights.
 Materials and methods: In a completely randomized design, 54 Arbor Acre broiler chicks aged 28 days old were allocated to two treatments. Each group included 27 chickens with three replicates (nine chickens per replication). The chickens were fed two diets, including basal diet (control) and basal diet with 5% dry matter BPLM for two weeks. 
 Results: The results of the nutrient composition of BPLM revealed 17.16% crude protein, 11.10% crude fiber, 1.70% ether extract, 7.10% ash, 39.0% nitrogen-free extract, 2413 metabolizable energy (kcal), 1.34% calcium, and 0.06% phosphorus. As a rich source of phytic acids, BPLM contains (14.69 mg/100g), tannins (3.23 mg/100 g), and oxalates (20 mg/100 g). The results showed that chickens fed a 5% BPLM-supplemented diet had lower feed intake but improved growth performance compared to the control. There was no significant difference in hematological and serum biochemical indices, carcass traits, cut-up parts, and relative organ weights.
 Conclusion: Incorporating BPLM into a finisher broiler diet decreases feed intake but improves growth performance. In addition, the results showed no effect on hematological and biochemical parameters or relative organ weights in chickens supplemented with BPLM.

Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter.

Radix Bupleuri exerts effective hepatoprotective and cholagogic effects through its Saikosaponins (SSs) component. Therefore, we attempted to determine the mechanism of saikosaponins used to promote bile excretion by studying their effects on intrahepatic bile flow, focusing on the synthesis, transport, excretion, and metabolism of bile acids. C57BL/6N mice were continuously gavaged with saikosaponin a (SSa), saikosaponin b2 (SSb2 ), or saikosaponin D (SSd) (200 mg/kg) for 14 days. Liver and serum biochemical indices were determined using Enzyme-linked immunosorbent assay (ELISA) kits. In addition, an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) was used to measure the levels of the 16 bile acids in the liver, gallbladder, and cecal contents. Furthermore, SSs pharmacokinetics and docking between SSs and farnesoid X receptor (FXR)-related proteins were analyzed to investigate the underlying molecular mechanisms. Administration of SSs and Radix Bupleuri alcohol extract (ESS) did not cause significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels. Saikosaponin-regulated changes in bile acid (BA) levels in the liver, gallbladder, and cecum were closely related to genes involved in BA synthesis, transport, and excretion in the liver. Pharmacokinetic studies indicated that SSs were characterized by rapid elimination (t1/2 as 0.68-2.47 h), absorption (Tmax as 0.47-0.78 h), and double peaks in the drug-time curves of SSa and SSb2 . A molecular docking study revealed that SSa, SSb2 , and SSd docked well with the 16 protein FXR molecules and target genes (<-5.2 kcal/mol). Collectively, saikosaponins may maintain BA homeostasis in mice by regulating FXR-related genes and transporters in the liver and intestine.

Salvianolic acid C promotes osteogenic differentiation of bone marrow mesenchymal stem cells in osteoporotic rats through activation of AMPK/SIRT1 pathway.

This study aimed to explore the molecular mechanism underlying the therapeutic effect of salvianolic acid C (SAC) on osteoporosis. Osteoporotic (OVX) rats were used as the model, and the impacts of SAC treatment on their serum and urine biochemical indicators were assessed. The biomechanical parameters of these rats were also evaluated. The effects of SAC treatment on the bone of OVX rats was quantified using hematoxylin & eosin staining and alizarin red staining, which reflect calcium deposition. The potential signaling pathway involved in SAC treatment was identified and confirmed through Western blotting, AMP-activated protein kinase (AMPK) inhibitors, and sirtuin-1 (small interfering RNA-SIRT1). The results showed that SAC could ameliorate the serum and urine biochemical metabolism, and the pathological alterations of bone tissue in OVX rats. SAC promoted the osteogenic differentiation of bone marrow mesenchymal cells in OVX rats, one of the key mechanisms for modulation of Runx2, Osx, and OCN, involved in the AMPK/SIRT1 signaling pathway. The findings from this study suggest that SAC promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in osteoporotic rats by activating the AMPK/SIRT1 pathway.

Study on the mechanism of Shuganzhi Tablet against nonalcoholic fatty liver disease and lipid regulation effects of its main substances in vitro

Ethnopharmacological relevanceShuganzhi Tablet (SGZT) originates from a famous traditional Chinese herbal formula Chaihu Decoction which can be applied to treat liver diseases, however, the pharmacodynamic mechanism of SGZT needs to be evaluated. Aim of this studyTo study the mechanism of SGZT in the treatment of non-alcoholic fatty liver disease (NAFLD), and screen out its effective ingredients. Materials and methodsIn this study, firstly, the main components of SGZT were analyzed qualitatively. And a rat model of NAFLD was established by feeding high-fat diet. Serum biochemical indexes and liver pathological analysis were used to evaluate the pharmacodynamic effect of SGZT in the treatment of NAFLD. In order to explore the pharmacodynamic mechanism, proteomics and metabolomics analysis were used. Western blotting was used to verify the expression of important differential proteins. And L02 cells were treated with free fatty acids (FFA) and the main substances of SGZT to establish the cell model of NAFLD in vitro and to reveal the pharmacodynamic substance of SGZT. ResultsTwelve components were detected in SGZT, and according to the results of serum biochemical indexes and liver pathological analysis, SGZT could effectively treat NAFLD. Combined with the results of bioinformatics analysis, we found that 133 differentially expressed proteins were reversed in liver samples of rats treated with SGZT. The important proteins in PPAR signaling pathway, steroid biosynthesis, cholesterol metabolism and fatty acid metabolism were mainly regulated to maintain cholesterol homeostasis and improve lipid metabolism. SGZT also affected various metabolites in rat liver, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and taurine. In addition, the main components contained in SGZT (hesperidin, polydatin, naringin, emodin, specnuezhenide, saikosaponin A) and a metabolite (resveratrol) could significantly reduce FFA-induced intracellular lipid accumulation. ConclusionSGZT effectively treated NAFLD, and PPAR-γ, Acsl4, Plin2 and Fads1 may be the main targets of SGZT. And Fads1-EPA/DHA-PPAR-γ may be the potential pharmacodynamic pathway. Cell experiments in vitro revealed that the main components of SGZT and their metabolites, such as hesperidin, polydatin, naringin, emodin, specnuezhenide, saikosaponin A and resveratrol may be the main components of its efficacy. Further research is needed to reveal and validate the pharmacodynamic mechanism.

Effects of Atmospheric Ammonia on Skeletal Muscle Growth in Broilers

Ammonia, one of the most polluted gases in poultry houses, has always been an urgent problem to solve. Exposure to ammonia can threaten the respiratory tract, induce inflammation, and decrease growth performance. To date, there are few studies investigating the effects of ammonia on skeletal muscle growth. In this experiment, a total of 144 broilers were randomly divided into two groups, and 0 ppm and 35 ppm atmospheric ammonia were administered in the chambers. The trial lasted for 21 days. The breast muscle, thigh muscle, dressed weight, and serum biochemical indexes were measured. The skeletal muscle fibre morphology was observed using light microscopy, and the expressions of genes associated with skeletal muscle development and myosin heavy chain genes were assessed. After 7 days of ammonia exposure, the broilers’ weight in the ammonia group decreased. On the 21st day of the experiment, in the ammonia group, the breast muscle weight, thigh muscle weight, and dressed weight decreased, the blood urea nitrogen content increased, skeletal muscle fibre diameter shortened, the expression of myostatin increased, and the expression of myosin heavy chain-FWM and myosin heavy chain-FRM decreased significantly. This article suggests that 35 ppm atmospheric ammonia seriously affects the skeletal muscle gain rate of broilers, and the myostatin pathway could be a potential regulation of the growth rate of muscle fibre under ammonia exposure.

Effects of Varying Levels of Lemon Grass Leaf Meal on Performance, Haematology and Serum Biochemical Indices of Broilers

A total of two hundred unsexed broiler chicks aged two weeks were used for six weeks feeding trial to evaluate growth performance, hematology, and serum biochemistry. In this study, broilers chicks were fed dietary lemon grass leaf meal at inclusion levels of T1control (0.00%), T2 (1.50%), T3 (2.25%) and T4 (3.75 %). The weighed broilers were distributed at random among the four treatment diets. A completely randomized experimental design was used, and each treatment was replicated five times with ten broilers per replicate. Experimental birds were provided experimental starter and finisher diets ad-libitum throughout the experimental period at weeks 2 to 4 and 5 to 7 respectively. The experiment revealed that weekly feed intake for week 2, 3, 4 and 6 was significantly affected (P&lt;0.05) except week five. The daily weight gain followed similar pattern, however significant difference were observed only in week 3, 4 and 7 in all the treatment groups. There were significant (P&lt;0.05) differences among the dietary groups in week 4, 6 and 7 in terms of feed conversion ratio. White blood cells value of birds fed on control diet 286.07x 109 /dl is similar to 283.37 and 268.67x 109 /dl for T3 and T4. Neutrophil values 14%, 19%,18% and 20% for T1, T2, T3 and T4 were statistically significant (P&lt;0.05) indicating that birds were challenged with increasing levels of lemon grass leaf meal beyond 3.75%. The results of this study indicate that birds fed with 1.5% of dietary lemon grass meal was the best among diets with lemon grass and comparable with the control group in terms of daily weight gain. This implies that birds fed with 1.5% level lemon grass leaf meal (LGLM) was able to utilize the experimental diet better than other treatment groups and without detrimental effects.

Production Performance and Serum Biochemical Indices as Influenced by Lysine and Methionine Supplementation to Low Protein Diet in Vanaraja Laying Hens

An experiment was conducted to evaluate the effect lysine and methionine supplementation to low protein diet on production performance and serum biochemical parameters in Vanaraja laying hens. One hundred twenty (n=120), 30-weeks old Vanaraja laying hens were randomly distributed into four dietary treatments with three replicates in each group having 10 birds in each replicate. Four diets were formulated with 2600 kcal/kg of metabolizable energy (ME) and 13% crude protein (CP). The dietary treatments were: T1- diet contains 0.65% lysine and 0.28% methionine; T2- diet contains 0.70% lysine and 0.32% methionine; T3- diet contains 0.75% lysine and 0.36% methionine and T4- diet contains 0.80% lysine and 0.40% methionine. Body weight and its changes, Hen Housed Egg Production (HHEP), egg weight (g), egg mass (g/day), and feed conversion ratio and serum biochemical parameters found significantly (P&lt;0.05) differed across the dietary treatments during different phases of the experimental period. There was significant (P&lt;0.05) effect of lysine and methionine on the overall body weight gain. Serum biochemical parameters like albumin, globulin, creatinine, uric acid, triglycerides and AST activity varied due to supplementation of EAAs to low CP diet. So it was concluded that diet containing 0.65% lysine and 0.28% methionine (T1) is adequate for optimum production performance and serum biochemical indices in Vanaraja laying hens.

Fecal metabonomics combined with 16S rDNA sequencing to analyze the changes of gut microbiota in rats fed with different protein source diets.

When blended, animal and plant proteins can complement each other in terms of amino acid composition and release time. In this study, we investigated whether the blended protein diet has a better feeding effect than the single protein diet, and to reveal the differences in growth and intestinal microbiota composition caused by the blended protein diet. Forty Sprague Dawley (SD) rats received diets with different protein sources, including casein (C), whey protein (WP), black soybean protein (BSP), and black soybean-whey blended protein (BS-WP), for eight weeks. To investigate the effects of blended protein supplement on gut microbiota and metabolites, we performed a high throughput 16S rDNA sequencing and fecal metabolomics profiling. In addition, we determined growth and serum biochemical indices, and conducted intestinal morphology analyses. Compared to those in the BSP and WP groups, the daily body weight gain and feed conversion efficiency increased in the BS-WP group. Serum biochemical indices indicated that the protein utilization efficiency of the WP and BS-WP groups was relatively high, and the BS-WP blended protein diet improved the protein adoption rate. The BS-WP blended protein diet also improved intestinal tissue morphology and promoted intestinal villi development compared to the single protein diets. Furthermore, dietary protein altered the composition of gut microbiota, the gut microbial diversity of rats fed with the BS-WP diet was significantly (P < 0.05) higher than that of the other groups. The difference in dietary protein corresponded with an alteration of fecal amino acids and their metabolites, and tryptophan and tyrosine metabolism were the key mechanisms leading to the changes in fecal microbial composition. Dietary protein sources played an important role in the growth and development of rats by influencing intestinal metabolism and microbial composition. The BS-WP blended protein diet was more conducive to nutrient absorption than the single protein diet. Furthermore, blended protein increased the diversity of intestinal microbes and aided the establishment of intestinal barrier function.

The involvement of antioxidant, stress, and immune-related genes in the responsive mechanisms of common carp (Cyprinus carpio) to hypersalinity exposure

Salinity stress is one of the marked influencing factors on the ecophysiology of aquaculture and is considered an important reason for the retreat of the fish industry. The current study is an endeavor to elucidate the molecular mechanisms that underlie the response to salinity stress in common carp. Fish (Average weight 5 ± 2 g) were randomly distributed into two groups; the 1st is a control was exposed to tap water (0.2 ppt salinity) and the 2nd is a treated was exposed to hypersalinity (10 ppt salinity) for five days. Serum biochemical indicators including total protein, albumin, globulins, A/G ratio, blood glucose, cortisone, Na+, K+, and Cl- levels were evaluated. Besides, Tumor necrosis factor-α, interleukin-1β, corticotropin-releasing hormone, and catalase enzyme mRNA expression levels were assessed in lymphoid and immunocompetent organs (liver and spleen) and osmoregulatory organs (kidney and gills) by using Real-time qPCR. Hypersalinity adversely affected the biochemical markers; total protein, albumin, and globulins decreased significantly; however, blood glucose, serum cortisol, and sodium markedly increased in fish exposed to hypersalinity compared with the control. In addition, from the molecular point of view, all the evaluated genes were upregulated at a high expression rate in the liver compared with other studied organs after the salinity challenge. On the contrary, hypersalinity modulated the expression of immune-related genes (Tumor necrosis factor-α and interleukin-1β) in the kidney and spleen and upregulated corticotropin-releasing hormone mRNA in all studied organs except gills. In conclusion, the obtained data clarified the molecular and biochemical mechanisms of salinity stress on the liver, kidney, spleen, and gills. Furthermore, it strongly suggests the implication of neural, endocrine, and immune systems in the responsive mechanisms to the salinity stress in carp.

Evaluation of Some Serum Biochemical Indices in Patients with Gestational Diabetes

The aim of this study was to evaluate some serum biochemical indices in patients with gestational diabetes. Among the study's participants were 100 expectant mothers ranging in age from 24 to 35 who had been diagnosed with diabetes at a maternity hospital or pregnancy center in Baghdad city. According to their previous menstrual cycle or an ultrasound, these ladies were between 28 and 33 weeks pregnant. There were two categories of pregnant women: Twenty pregnant women in good health comprised (control group). Eighty GDM-pregnant women were enrolled. The current results showed a significant increase in levels of glucose, cholesterol, triglyceride, ALT, bilirubin, uric acid, and creatinine in the GDM group as compared with control patients, also a significant decrease in the levels of Albumin, HDL in GDM group as compared with control group. There were no significant differences in the levels of urea and AST in both GDM and control groups. In conclusion, there was a significant increase in levels of glucose, cholesterol, triglyceride, ALT, bilirubin, uric acid, and creatinine in the GDM group.

Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered &quot;non-toxic&quot; TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P&lt;0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Inhibition of MAOB Ameliorated High-Fat-Diet-Induced Atherosclerosis by Inhibiting Endothelial Dysfunction and Modulating Gut Microbiota.

In this study, monoamine oxidase B (MAOB) was activated under pathological conditions, and was the novel source of cardiovascular reactive oxygen species (ROS). ROS-induced endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, whether MAOB regulates endothelial oxidative stress and its related mechanism and whether gut microbiota mediates the anti-atherosclerosis effect of MAOB inhibitor remains unclear. In our study, MAOB expressions were elevated in high-fat diet (HFD) fed mice aortas, but only in vascular endothelial cells (not in smooth muscle cells). MAOB small interfering RNA significantly attenuated the palmitic-acid (PA)-induced endothelial oxidative stress and dysfunction. Furthermore, RNA-sequencing data revealed that MAOB knockdown decreased the levels of proinflammatory and apoptotic gene induced by PA. Microarray analysis and qPCR assay showed that miR-3620-5p was significantly decreased under the HFD condition. The dual-luciferase reporter, Western blot and qPCR assay confirmed that miR-3620-5p directly regulated MAOB by binding to its mRNA 3'UTR. Moreover, inhibition of MAOB by selegiline significantly ameliorated endothelial dysfunction and reduced atherosclerotic burden in HFD-fed ApoE-/- mice. Finally, 16S rRNA sequencing showed that selegiline significantly altered the community compositional structure of gut microbiota. Specifically, selegiline treatment enriched the abundance of Faecalibaculum and Akkermansia, decreased the abundance of unclassified_f__Lachnospiraceae, Desulfovibrio, and Blautia, and these genera were significantly correlated with the serum biochemical indices. Taken together, our findings showed that MAOB controlled endothelial oxidative stress homeostasis, and revealed the anti-atherosclerotic effect of selegiline by ameliorating endothelial dysfunction and modulating the composition and function of gut microbiota.

The Requirement and Protective Effects of Dietary Protein against Chronic Ammonia Exposure in Juvenile Genetically Improved Farmed Tilapia (Oreochromis niloticus).

Ammonia is a key risk factor in intensive aquaculture systems. This experiment is aimed at investigating the influence of dietary protein levels on genetically improved farmed tilapia (GIFT, Oreochromis niloticus) under chronic ammonia stress. GIFT juveniles of 4.00 ± 0.55 g were exposed to high ammonia level at 0.88 mg/L and fed with six diets comprising graded protein levels at 22.64%, 27.26%, 31.04%, 35.63%, 38.47%, and 42.66% for 8 weeks. The fish in negative control was fed the diet with 31.04% protein in normal water (0.02 mg ammonia/L water). Our results showed that high ammonia exposure (0.88 mg/L) caused significant decrease in fish growth performance, hematological parameters, liver antioxidant enzymes (catalase and glutathione peroxidase), and gill Na+- and K+-dependent adenosine triphosphatase (Na+/K+-ATP) activity. When fish were under high ammonia exposure, the weight gain rate, special growth rate, feed efficiency, and survival rate elevated significantly with dietary protein supplementation increase to 35.63%, whereas protein efficiency ratio, hepatosomatic index, and viscerosomatic index showed a decreased tendency. Dietary protein administration significantly enhanced crude protein but reduced crude lipid contents in the whole fish. Fish fed diets with 35.63%-42.66% protein had higher red blood cell counts and hematocrit percentage than fish fed 22.64% protein diet. The values of serum biochemical indices (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase), hepatic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and gill Na+/K+-ATP activity were all elevated with the increment of dietary protein. Moreover, histological analysis indicated that dietary protein administration could prevent the ammonia-induced damages in fish gill, kidney, and liver tissues. Based on weight gain rate as a response criterion, the optimal dietary protein requirement for GIFT juveniles under chronic ammonia stress was 37.9%.

Effect of Ornithine α-Ketoglutarate on Intestinal Microbiota and Serum Inflammatory Cytokines in Dextran Sulfate Sodium Induced Colitis.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.

PFOA exposure induces aberrant glucose and lipid metabolism in the rat liver through the AMPK/mTOR pathway

Perfluorooctanoic acid (PFOA) is the most prominent member of a widely utilized family of compounds named Perfluoroalkyl substances (PFASs). Initially produced for use in both industrial and consumer applications, it has since been recognized that PFASs are extremely persistent in the environment where they have been characterized as persistent organic pollutants (POPs). While previous studies have demonstrated that PFOA may induce disorders of lipid and carbohydrate metabolism, the precise mechanisms by which PFOA produces this phenotype and the involvement of downstream AMPK/mTOR pathways remains unclear. In this study, male rats were exposed to 1.25, 5 and 20 mg PFOA/kg body weight/day for 28 days by oral gavage. After 28 days, blood was collected and tested for serum biochemical indicators and livers were removed and weighed. To investigate aberrant metabolism in rats exposed to PFOA, livers were analyzed by performing LC-MS/MS untargeted metabolomics, quantitative real-time PCR, western blotting, immunohistochemical staining was also performed on exposed tissues. Our results showed that exposure to PFOA induced liver damage, increased the expression of glucose and lipid related biochemical indexes in liver and serum, and altered the expression levels of AMPK/mTOR pathway related genes and proteins. In summary, this study clarifies the mechanisms responsible for PFOA toxicity in the liver of exposed animals.

Dietary Fishmeal Can Be Partially Replaced with Non-Grain Compound Proteins through Evaluating the Growth, Biochemical Indexes, and Muscle Quality in Marine Teleost Trachinotus ovatus.

In the context of human food shortages, the incorporation of non-grain feedstuff in fish feed deserves more research attention. Here, the feasibility and appropriate ratio of non-grain compound protein (NGCP, containing bovine bone meal, dephenolized cottonseed protein, and blood cell meal) for dietary fishmeal (FM) replacement were explored in golden pompano (Trachinotus ovatus). Four isonitrogenous (45%) and isolipidic (12%) diets (Control, 25NGP, 50NGP, and 75NGP) were prepared. Control contained 24% FM, whereas the FM content of 25NGP, 50NGP, and 75NGP was 18%, 12%, and 6%, respectively, representing a 25%, 50%, and 75% replacement of FM in Control by NGCP. Juvenile golden pompano (initial weight: 9.71 ± 0.04 g) were fed the four diets for 65 days in sea cages. There was no significant difference between the 25NGP and Control groups in terms of weight gain, weight gain rate, and specific growth rate; contents of crude protein, crude lipid, moisture, and ash in muscle and whole fish; muscle textural properties including hardness, chewiness, gumminess, tenderness, springiness, and cohesiveness; and serum biochemical indexes including total protein, albumin, blood urea nitrogen, HDL cholesterol, total cholesterol, and triglycerides. However, the golden pompano in 50NGP and 75NGP experienced nutritional stress, and thus some indicators were negatively affected. In addition, compared to the Control group, the expression levels of genes related to protein metabolism (mtor, s6k1, and 4e-bp1) and lipid metabolism (pparγ, fas, srebp1, and acc1) of the 25NGP group showed no significant difference, but the 4e-bp1 and pparγ of the 75NGP group were significantly upregulated and downregulated, respectively (p < 0.05), which may explain the decline in fish growth performance and muscle quality after 75% FM was replaced by NGCP. The results suggest that at least 25% FM of Control can be replaced by NGCP, achieving a dietary FM content of as low as 18%; however, the replacement of more than 50% of the dietary FM negatively affects the growth and muscle quality of golden pompano.