Gene Expression Of Pro-inflammatory Factors Research Articles

Effect of rhamnogalacturonan-I-rich polysaccharides isolated from crabapple hydrolysates on IL-1β-induced inflammation in intestinal epithelial cells

This study aimed to investigate the structural characteristics and intracellular mechanisms of polysaccharides (MP-PE-I) purified from a crabapple (Malus prunifolia) enzymatic hydrolysate (MP-PE). Activity-guided fractionation revealed that MP-PE-I was the active moiety and significantly reduced the production and gene expression of pro-inflammatory factors in interleukin (IL)-1β-treated intestinal epithelial cells (Caco-2). Moreover, MP-PE-I downregulated the phosphorylation and nuclear localization of proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, as evidenced by immunoblotting and immunofluorescence analysis. In antagonistic studies with specific inhibitors of the MAPK and NF-κB pathways, IL-6 inhibition was significantly regulated by p38; IL-8 by IκBα, JNK, and p38; and monocyte chemoattractant protein-1 (MCP-1) by JNK, p38, and ERK. Additionally, MP-PE-I significantly decreased the mRNA and protein expression of IL-1 receptor type 1. Chemical and structural characteristic analyses showed that MP-PE-I is a polysaccharide rich in rhamnogalacturonan (RG)-I and plays a crucial role in intestinal immunomodulation. To our knowledge, this is the first study to demonstrate the intestinal immunomodulatory activity, intracellular mechanisms, and structural characteristics of RG-I-rich polysaccharides isolated from crabapples.

Effects of cold acclimation on serum biochemical parameters and metabolite profiles in Schizothorax prenanti

BackgroundEnvironmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation.ResultsIn this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P < 0.05) increased, and the level of glucose was significantly (P < 0.05) decreased under cold acclimation. Cold acclimation had no effect on the gene expression of pro-inflammatory factors and anti-inflammatory factors of S. prenanti. Metabolomics analysis by LC-MS showed that a total of 60 differential expressed metabolites were identified after cold acclimation, which involved in biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, steroid degradation, purine metabolism, and citrate cycle pathways.ConclusionThe results indicate that cold acclimation can alter serum metabolites and metabolic pathways to alter energy metabolism and provide insights for the physiological regulation of cold-water fish in response to cold acclimation.

Improvement of sea buckthorn (Hippophae rhamnoides L.) flavonoids on the antioxidant and immune performance of Yellow River carp (Cyprinus carpio L.) fed high-carbohydrate diet

High-carbohydrate (HC) diets may lead to the deterioration of the antioxidant and immune properties of Yellow River carp and the healthy development of the industry. Studies in mammals have found that sea buckthorn flavonoids (SF) improve antioxidant and immune performance. Therefore, this study comprehensively evaluated the effects of SF on Yellow River carp using in vitro and feeding trials with an HC diet. Control (C, 27.23 %), high-carbohydrate (HC, 42.99 %), and HC + SF (0.1 %, 0.2 %, and 0.4 %) groups were studied in a 10-week aquaculture experiment. The main findings were as follows: (1) SF scavenged O2·‐, ·OH, and DPPH free radicals in vitro, which gradually increased with the SF concentration. (2) The antioxidant and immune performance of Yellow River carp was enhanced by dietary supplementation with SF, which involved the regulation of activities of antioxidant and immune enzymes, as well as their changes at the transcription and protein levels. In terms of antioxidant properties, compared to the HC group, HC + SF significantly decreased the activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase and the contents of H2O2 and malondialdehyde in the serum and hepatopancreas. The activities of glutathione, glutathione-Px, superoxide dismutase, catalase, and total antioxidant activity in the HC-diet group. In contrast, the addition of SF increased antioxidant enzyme activity. In the hepatopancreas and muscles, SF regulated and activated Nrf2-Keap1, a key signaling pathway for oxidative stress. SF significantly increased the mRNA expression levels of downstream genes (gr, ho-1, cat, and sod) regulated by nrf2. In terms of immune performance, 0.4 % SF markedly increased the activity of immune-related enzymes. SF inhibited the gene expression of pro-inflammatory factors induced by the HC diet and promoted the gene expression of anti-inflammatory factors. In addition, the resistance of Yellow River carp to Aeromonas hydrophila was enhanced by SF. In summary, SF supplementation can reduce oxidative stress and inflammatory harm caused by the HC diet and improve the antioxidant and immune performance of Yellow River carp to varying degrees.

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology.

Paederia scandens is a natural medicinal plant that is widely used for its various pharmacological effects including antiviral, antitumor, anti-inflammatory, and antibacterial activities. However, there is no scientific evidence to support its antidiarrheal effect. In this study, the antidiarrheal activity of P. scandens was evaluated using several validated models. By using HPLC-ESI-MS in conjunction with a network pharmacology approach, the possible antidiarrheal mechanisms of P. scandens active fragments were studied, and they were subsequently verified in a mouse model of diarrhea. Finally, utilizing molecular docking, active compounds that might have antidiarrheal properties were hypothesized. The results show that the main antidiarrheal part of P. scandens has 10 chemical components in the n-butanol fraction (PSNB). The key targets of PSNB and diarrhea, EGFR, AKT1, and PIK3CA, were screened by network pharmacology analysis. And the mechanism of PSNB in the treatment of diarrhea may be highly related to the EGFR tyrosine kinase inhibitor resistance and PI3K/AKT signaling pathway. Besides, through the qRT-PCR and western-blot experiments, it was found that PSNB could inhibit the gene expression of proinflammatory factors by reducing the protein expression of AKT1 and PI3K and regulating the NF-κB signaling pathway in mice. In addition, asperuloside, paederosidic acid, paederoside, paederosidic acid methyl ester, and 6'-O-E-feruloylmonotropein have better docking energies than other chemical components in PSNB with EGFR, AKT1, and PIK3CA. In conclusion, the main antidiarrheal active site of P. scandens is the n-butanol site. PSNB may exert an antidiarrheal effect by regulating the PI3K/Akt/NF-κB signaling pathway. Among them, asperuloside, paederosidic acid, paederoside, paederosidic acid methyl ester, and 6'-O-E-feruloylmonotropein may be the active ingredients that exert an antidiarrheal effect.

Effects of Oat Bran Addition on the Growth Performance and Intestinal Health of Nile Tilapia (Oreochromis niloticus) Exposed to Copper Ions.

This study investigated the effects of the oat bran addition on the growth performance and intestinal health of Nile tilapia (Oreochromis niloticus) exposed to copper ions. Four groups of diets containing 0%, 5%, 10%, and 20% oat bran were fed to Nile tilapia for four weeks. The results showed that oat bran had a dose-dependent effect on the growth performance of Nile tilapia. The addition of oat bran can increase the relative abundance of Delftia, which is capable of degrading heavy metals in the intestinal tract and alleviating the intestinal damage caused by copper ion stress. Compared to the control group, the 5% oat bran group had an increased intestinal antioxidant capacity. The relative gene expression of proinflammatory factors (NF-κB, IL-1β) was significantly downregulated in the 5% oat bran group (P < 0.05), and the relative gene expression of anti-inflammatory factors (TGF-β), HIF-1α, occludin, and claudin was significantly upregulated (P < 0.05). In conclusion, we suggest that 5% oat bran should be added to the diet to improve the growth performance of Nile tilapia and alleviate the negative effects of copper ion stress on intestinal health.

Radix Panacis quinquefolii Extract Ameliorates Inflammatory Bowel Disease through Inhibiting Inflammation.

To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P&lt;0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P&lt;0.05 or P&lt;0.01). RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

Peripheral NF-\u03baB dysregulation in people with schizophrenia drives inflammation: putative anti-inflammatory functions of NF-\u03baB kinases

Elevations in plasma levels of pro-inflammatory cytokines and C-reactive protein (CRP) in patient blood have been associated with impairments in cognitive abilities and more severe psychiatric symptoms in people with schizophrenia. The transcription factor nuclear factor kappa B (NF-κB) regulates the gene expression of pro-inflammatory factors whose protein products trigger CRP release. NF-κB activation pathway mRNAs are increased in the brain in schizophrenia and are strongly related to neuroinflammation. Thus, it is likely that this central immune regulator is also dysregulated in the blood and associated with cytokine and CRP levels. We measured levels of six pro-inflammatory cytokine mRNAs and 18 mRNAs encoding NF-κB pathway members in peripheral blood leukocytes from 87 people with schizophrenia and 83 healthy control subjects. We then assessed the relationships between the alterations in NF-κB pathway genes, pro-inflammatory cytokine and CRP levels, psychiatric symptoms and cognition in people with schizophrenia. IL-1β and IFN-γ mRNAs were increased in patients compared to controls (both p < 0.001), while IL-6, IL-8, IL-18, and TNF-α mRNAs did not differ. Recursive two-step cluster analysis revealed that high levels of IL-1β mRNA and high levels of plasma CRP defined ‘high inflammation’ individuals in our cohort, and a higher proportion of people with schizophrenia were identified as displaying ‘high inflammation’ compared to controls using this method (p = 0.03). Overall, leukocyte expression of the NF-κB-activating receptors, TLR4 and TNFR2, and the NF-κB subunit, RelB, was increased in people with schizophrenia compared to healthy control subjects (all p < 0.01), while NF-κB-inducing kinase mRNAs IKKβ and NIK were downregulated in patients (all p < 0.05). We found that elevations in TLR4 and RelB appear more related to inflammatory status than to a diagnosis of schizophrenia, but changes in TNFR2 occur in both the high and low inflammation patients (but were exaggerated in high inflammation patients). Further, decreased leukocyte expression of IKKβ and NIK mRNAs was unique to high inflammation patients, which may represent schizophrenia-specific dysregulation of NF-κB that gives rise to peripheral inflammation in a subset of patients.

The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence.

Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted “sterile inflammatory reaction” positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction.

Mycotoxins binder supplementation alleviates aflatoxin B1 toxic effects on the immune response and intestinal barrier function in broilers

This experiment was conducted to evaluate whether a commercial mycotoxins-binder, XL, could effectively attenuate the negative effects of Aflatoxin B1 (AFB1) on growth performance, immunological function, and intestinal health in birds. Two hundred forty 1-day-old Arbor Acres broiler chickens were randomly divided into 4 treatments using a 2 × 2 factorial randomized design with 2 levels of dietary mycotoxins binder (0 or 2g /kg) and 2 AFB1 supplemented levels (0 or 200 μg/kg) from 0 to 42 d. Results showed that AFB1 exposure impaired growth performance by decreasing BWG in 1–21 d and 1–42 d, decreasing FI in 1–21 d, increasing FCR in 1–21 d and 1–42 d (P < 0.05). Broilers fed AFB1- contaminated diet impaired the immune function, as evident by decreasing IgA contents, Newcastle disease antibody titers in serum, and sIgA contents of jejunal mucosa at 21 d (P < 0.05). On the other hand, AFB1 challenge significantly increased the gene expression of proinflammatory factors in spleen at 21 d and liver at 42 d, and significantly decreased claudin-1 expression at 42 d and occludin expression at 21 d, and increased claudin-2 at 21 d in jejunum of broiler chickens (P < 0.05) compared to the basal diet group. Dietary XL supplementation significantly decreased the gene expression of IL-6 in spleen at 21 d and IL-1β in liver at 42 d, cytochrome P450 3A4 (CYP3A4) expression in liver at 21 d of broilers (P < 0.05) compared with the nonsupplemented birds, regardless of AFB1 challenged or not. Inclusion of 2 g/kg XL increased serum ALB at 42 d, IgM and IgA at 42 d, Newcastle disease antibody titer level at 35 d (P < 0.05). Dietary XL addition enhanced intestinal barrier function by increasing the expression of claudin-1 at 21 d and Occludin at 42 d (P < 0.05) in jejunum. Conclusively, 2 g/kg mycotoxins-binder can relieve the toxic effect of AFB1 on broilers.

Activation of Autophagy Relieves Linoleic Acid-Induced Inflammation in Large Yellow Croaker (Larimichthys crocea).

High levels of soybean oil (SO) in fish diets enriched with linoleic acid (LA, 18:2n-6) could induce strong inflammation. However, the molecular mechanism underlying LA-induced inflammation in the liver of large yellow croaker (Larimichthys crocea) has not been elucidated. Based on previous research, autophagy has been considered a new pathway to relieve inflammation. Therefore, the present study was performed to investigate the role of autophagy in regulating LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro. The results of the present study showed that activation of autophagy in liver or hepatocytes could significantly reduce the gene expression of proinflammatory factors, such as tumor necrosis factor α (TNFα) and interleukin 1β (IL1β). The results of the present study also showed that inhibition of autophagy could upregulate the gene expression of proinflammatory factors and downregulate the gene expression of anti-inflammatory factors in vivo and in vitro. Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression in vivo and in vitro, while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro for the first time, which may offer considerable benefits to the aquaculture industry and human health.

Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson's Disease.

Parkinson’s disease (PD) is considered the most common disorder of synucleinopathy, which is characterised by intracellular inclusions of aggregated and misfolded α-synuclein (α-syn) protein in various brain regions, and the loss of dopaminergic neurons. During the early prodromal phase of PD, synaptic alterations happen before cell death, which is linked to the synaptic accumulation of toxic α-syn specifically in the presynaptic terminals, affecting neurotransmitter release. The oligomers and protofibrils of α-syn are the most toxic species, and their overexpression impairs the distribution and activation of synaptic proteins, such as the SNARE complex, preventing neurotransmitter exocytosis and neuronal synaptic communication. In the last few years, the role of the immune system in PD has been increasingly considered. Microglial and astrocyte activation, the gene expression of proinflammatory factors, and the infiltration of immune cells from the periphery to the central nervous system (CNS) represent the main features of the inflammatory response. One of the actors of these processes is α-syn accumulation. In light of this, here, we provide a systematic review of PD-related α-syn and inflammation inter-players.

Development of a PHBV nanoparticle as a peptide vehicle for NOD1 activation

NOD1 is an intracellular receptor that, when activated, induces gene expression of pro-inflammatory factors promoting macrophages and neutrophils recruitment at the infection site. However, iE-DAP, the dipeptide agonist that promotes this receptor's activation, cannot permeate cell membranes. To develop a nanocarrier capable of achieving a high and prolonged activation over time, iE-DAP was encapsulated in nanoparticles (NPs) made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The physicochemical properties, colloidal stability, encapsulation efficiency, and cellular uptake of iE-DAP-loaded PHVB NPs were analyzed. Results evidenced that physicochemical properties of iE-DAP-loaded NPs remained stable over time, and NPs were efficiently internalized into cells, a process that depends on time and concentration. Moreover, our results showed that NPs elicited a controlled cargo release in vitro, and the encapsulated agonist response was higher than its free form, suggesting the possibility of activating intracellular receptors triggering an immune response through the release of NOD1 agonist.

Preparation and Evaluation of IL-1ra-Loaded Dextran/PLGA Microspheres for Inhibiting Periodontal Inflammation In Vitro.

Periodontitis is a chronic infectious disease, the course and progression of which are determined by the interaction between microorganisms and the host. Interleukin 1β plays an important role in the destruction of periodontal tissues. Interleukin 1 receptor antagonist (IL-1ra) can inhibit the biological activity of IL-1β without triggering any intracellular signaling. This study aimed to prepare IL-1ra-loaded dextran/PLGA microspheres and evaluate the physical and chemical characteristics and anti-inflammatory properties. Results suggested that the microspheres can be easily prepared into a drug carrier with good biocompatibility and can effectively inhibit the gene expression of pro-inflammatory factors induced by IL-1β in human gingival fibroblasts. Hence, the microspheres are excellent candidate for periodontitis treatment.

Cerebrolysin Ameliorates Focal Cerebral Ischemia Injury Through Neuroinflammatory Inhibition via CREB/PGC-1α Pathway.

Neuroinflammation is one of the important factors aggravating brain injury after ischemic stroke. We aimed to investigate the effects of cerebrolysin (CBL) on neuroinflammation in vivo and in vitro and the underlying mechanisms. The gene expressions of pro-inflammatory factors and anti-inflammatory factors were analyzed by real time PCR in rat transient middle cerebral artery occlusion (tMCAO) model, lipopolysaccharides-induced neuroinflammatory mice model and LPS-treated mouse primary microglia cells. The neuroprotective effects of CBL were evaluated by infarct size, Longa test and Rotarod test for long-term functional recovery in rats subjected to ischemia. The role of CREB/PGC-1α pathway in anti-neuroinflammatory effect of CBL was also determined by real time PCR and Western blotting. In the tMCAO model, administration of CBL at 3 h post-ischemia reduced infarct volume, promoted long-term functional recovery, decreased the gene expression of pro-inflammatory factors and increased the gene expression of anti-inflammatory factors. Correspondingly, in LPS-induced neuroinflammatory mice model, CBL treatment attenuated sickness behavior, decreased the gene expression of pro-inflammatory factors, and increased the gene expression of anti-inflammatory factors. In in vitro and in vivo experiments, CBL increased the protein expression levels of PGC-1α and phosphorylated CREB to play anti-inflammatory effect. Additionally, the application of the specific CREB inhibitor, 666-15 compound could effectively reverse the anti-inflammatory effect of CBL in primary mouse microglia cells and anti-ischemic brain injury of CBL in rats subjected to tMCAO. In conclusion, CBL ameliorated cerebral ischemia injury through reducing neuroinflammation partly via the activation of CREB/PGC-1α pathway and may play a therapeutic role as anti-neuroinflammatory agents in the brain disorders associated with neuroinflammation.

Chronic inflammation is a key to inducing liver injury in blunt snout bream (Megalobrama amblycephala) fed with high-fat diet

The aim of this article is to investigate the mechanism of lipotoxicity induced by high-fat diets (HFD) in Megalobrama amblycephala. In the present study, fish (average initial weight 40.0 ± 0.35 g) were fed with two fat levels (6% and 11%) diets with four replicates for 60 days. At the end of the feeding trial, fish were challenged by thioacetamide (TAA) and survival rate was recorded for the next 96 h. The result showed that long-term HFD feeding induced a significant increase (P < 0.05) in the levels of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) in plasma. In addition, liver histopathological analysis showed an increased dilation of the blood vessels, erythrocytes outside of the blood vessels and vacuolization in fish fed with high-fat diet. After TAA challenge, compared with group fed with normal-fat diets (NFD), fish fed with HFD showed a significantly (P < 0.05) low survival rate. After feeding Megalobrama amblycephala with HFD for 60 days, the protein content and gene expression of pro-inflammatory factors were significantly elevated (P < 0.05). The protein and gene relative expressions of a Caspase-3, Caspase-9 and CD68 were significantly increased (P < 0.05), while antioxidant-related enzyme activities were significantly reduced (P < 0.05) in the liver of fish fed with HFD. In addition, HFD feeding also induced genotoxicity. Comet assay showed a significantly (P < 0.05) elevated DNA damage in blunt snout bream fed with HFD. Compared with normal-fat diets (NFD) group, the protein expression of γH2AX and gene expressions involved in cell cycle arrest were significantly increased (P < 0.05) in fish fed with HFD. Data in this research showed that lipotoxicity induced by HFD was likely mediated by chronic inflammation regulating macrophage recruitment, apoptosis and DNA damage. The study was valuable to understand the mechanism by which liver injury is induced in fish fed with HFD.

Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice.

The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect.

Changing the content of histone proteins and heat-shock proteins in the blood and liver of rats after the single and repeated administration of nanocluster iron-molybdenum polyoxometalates

The effect of nanocluster iron-molybdenum polyoxometallates (POMs) on the content of histone proteins and heat shock proteins in rat blood and liver after single and repeated administration had been investigated. It is found that the introduction of POMs was not accompanied by a decrease in the number of histone proteins in blood lymphocytes, which may indicate a lack of gene expression of proinflammatory factors. An increase in the content of the heat shock protein Hsp60 and Hsp70 in the liver is revealed, and the degree of increase depended on the nanoparticles exposition. The assumptions about the absence of a lymphocytes proinflammatory phenotype and the heat shock proteins protective effect are confirmed with the continuation of normal functional-state liver parameters during all periods of polyoxometalates exposure.

Impaired adipogenesis in adipose tissue associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet.

Chronic inflammation might be associated with hepatic lipid deposition independent of overnutrition. However, the mechanism is not fully understood. In this study, we investigate if impaired adipogenesis in adipose tissue is associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet. Casein injection in C57BL/6J mice was given every other day to induce chronic inflammation. All mice were sacrificed after 18weeks of injections. The serum, liver and adipose tissue were collected for analysis. Real-time polymerase chain reaction and western blotting were used to examine the gene and protein expressions of molecules involved in hepatic lipid metabolism and adipose adipogenesis. Casein injection elevated serum levels of insulin, free fatty acid (FFA) and proinflammatory factors. The gene expression of proinflammatory factors of adipose tissue and the liver also increased in the casein group as compared with the control group. Chronic inflammation up-regulated the hepatic expression of fatty acid translocase (CD36) and down-regulated microsomal triacylglycerol transfer protein (MTP), carnitine palmitoyltransferase 1a (CPT1a) and acyl-coenzyme a oxidase 1 (ACOX1). Meanwhile, chronic inflammation not only diminished the size of adipocytes, but also down-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteinα (C/EBPα), both indicating an impaired adipogenesis. Besides disturbed lipid metabolism in the liver per se, impaired adipogenesis in the adipose tissue might also be associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet.

Effects of Probiotic Yogurt on Fat Distribution and Gene Expression of Proinflammatory Factors in Peripheral Blood Mononuclear Cells in Overweight and Obese People with or without Weight-Loss Diet

Objectives: The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets.Methods: A total of 75 healthy overweight and obese individuals completed this randomized doubled-blind controlled clinical trial. Participants were randomly assigned to groups consuming regular yogurt with a low-calorie diet (LCD, RLCD; n = 25) or receiving probiotic yogurt with LCD (PLCD; n = 25) or consuming probiotic yogurt without LCD (PWLCD; n = 25) for 8 weeks. The pribiotic regimen contained 200 g/day yogurt, enriched by Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 108 colony-forming units/g. Body fat percentage, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), leptin, and mRNA levels of inflammation-related genes (TNF-α and RAR-related orphan receptor gamma [ROR-γt]) in peripheral blood mononuclear cells (PBMCs) were measured.Results: A reduction in body mass index (BMI), fat percentage, and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt. Reduction in the gene expression of ROR-γt was significant in the PLCD group (p < 0.001). The expression of TNF-α did not change among all groups after intervention. The mean concentration of leptin was significantly decreased in all groups after the dietary intervention, but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups (−2.38, p < 0.001 [PLCD] vs −1.75, p = 0.002 [RLCD] and −0.55 ng/mL, p = 0.12 [PWLCD]). The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention (−3.4, p = 0.03 vs −1.76, p < 0.001 and −2.98 pg/mL, p < 0.001, respectively).Conclusion: Our results suggested that the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in PBMCs, fat percentage, and body weight among overweight and obese individuals.

Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Obesity is a major risk factor for the development of osteoarthritis (OA) that is associated with a state of low-grade inflammation and increased circulating levels of adipokines and free fatty acids (FFAs). The aim of this study was to analyze the effects of saturated (palmitate) and monounsaturated (oleate) FFAs on articular chondrocytes, synoviocytes, and cartilage. Human articular chondrocytes and fibroblast-like synoviocytes obtained from young healthy donors and OA chondrocytes from patients undergoing total knee replacement surgery were treated with palmitate or oleate alone or in combination with interleukin-1β (IL-1β). Cell viability, caspase activation, and gene expression of proinflammatory factors, extracellular matrix (ECM) proteins, and proteases were studied. In addition, chondrocyte viability, IL-6 production, and matrix damage were assessed in bovine and human articular cartilage explants cultured with FFAs in the presence or absence of IL-1β. Palmitate, but not oleate, induced caspase activation and cell death in IL-1β-stimulated normal chondrocytes, and up-regulated the expression of IL-6 and cyclooxygenase 2 in chondrocytes and fibroblast-like synoviocytes through Toll-like receptor 4 (TLR-4) signaling. In cartilage explants, palmitate induced chondrocyte death, IL-6 release, and ECM degradation. Palmitate synergized with IL-1β in stimulating proapoptotic and proinflammatory cellular responses. Pharmacologic inhibition of caspases or TLR-4 signaling reduced palmitate and IL-1β induced cartilage damage. Palmitate acts as a proinflammatory and catabolic factor that, in synergy with IL-1β, induces chondrocyte apoptosis and articular cartilage breakdown. Collectively, our data suggest that elevated levels of saturated FFAs that are often found in patients who are obese may contribute to the pathogenesis of OA.