Tumor Necrosis Factor-alpha Expression Research Articles

Biomodulation of Induced Tooth Movement by Three Methods, Corticopuncture, Photobiomodulation, and Their Combination: An Animal Study.

Objective: The aim of this study was to assess the effects of accelerated tooth movement (ATM) methods: corticopuncture (CP), photobiomodulation (PBM), and their combination (CP + PBM) by evaluating tooth displacement, alveolar bone changes, and molecular and cellular response compared with conventional induced tooth movement. Materials and methods: Tooth movement and bone changes were evaluated on days 1, 3, and 7 (9 animals per time point) using microtomography, histological, and immunohistochemical evaluation, at compression and tension sites. CP groups received two perforations in the palate and one mesial to the molars. PBM was performed using GaAlAs diode laser applied every other day for 7 days (λ = 808 nm, 100 mW) in two points for 15 sec/point and total energy of 3 J. Results: Tooth movement was significantly increased in all three ATM groups after 7 days compared with the control group (mean 0.24 mm) by 27% PBM (0.31 mm), 45% CP (0.35 mm), and 57% CP + PBM (0.38 mm) (p < 0.05). At the compression side, all ATM groups showed significant decrease in bone density on day 3 (p < 0.05) and significant less bone volume on day 7 compared with Control (p < 0.05). At the tension side, PBM group showed a significant increase in bone density and volume on day 3 (p < 0.05). Immunohistochemistry analysis showed that at the compression side, tartrate-resistant acid phosphatase-positive cells, RANKL, and tumor necrosis factor-alpha expression were highly marked of the PBM and the combined method groups (p < 0.05). PBM and CP + PBM groups showed a significant increase in expression Runt-related transcription factor 2 and osterix (p < 0.05) at the tension side. Conclusions: All ATM groups showed increase on tooth displacement with CP + PBM group showing greatest tooth displacement. CP method appears to stimulate bone catabolism, PBM has more effect on bone formation, and the combined method showing a synergistic effect on bone remodeling.

Porphyromonas gingivalis exacerbates alcoholic liver disease by altering gut microbiota composition and host immune response in mice.

Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, increases the risk of systemic diseases. P. gingivalis infection is closely associated with alcoholic liver disease (ALD), but the underlying mechanism remains unclear. We aimed to investigate the role of P. gingivalis in the pathogenesis of ALD. An ALD mouse model was established using a Lieber-DeCarli liquid diet, and C57BL/6 mice were treated with P. gingivalis to detect the pathological indicators of ALD. Oral administration of P. gingivalis exacerbated alcohol-induced alterations in the gut microbiota, leading to gut barrier dysfunction and inflammatory response and disruption of the T-helper 17 cell/T-regulatory cell ratio in the colon of ALD mice. Furthermore, P. gingivalis worsened liver inflammation in ALD mice by increasing the protein expression of toll-like receptor 4 (TLR4) and p65, increasing the mRNA expression of interleukins-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) and up-regulating the transforming growth factor-beta 1 (TGF-β1) and galectin-3 (Gal-3) production. These results indicate that P. gingivalis accelerates the pathogenesis of ALD via the oral-gut-liver axis, necessitating a new treatment strategy for patients with ALD complicated by periodontitis.

The protective effects of silymarin nanoemulsion on 5-fluorouracil-induced gastrointestinal toxicity in rats

5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg−1), SM (5 mg.kg−1), 5FUra + SMN (5 mg.kg−1), and 5FUra + SM (5 mg.kg−1) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg−1) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra.

The Effect of Eight Weeks of Resistance Training and Testosterone Enanthate Consumption on TNF-α and IL-6 Genes’ Expression in the Kidney Tissue of Female Wistar Rats

Objectives: This study aimed to evaluate the effect of a testosterone enanthate anabolic steroid on the gene expression of inflammatory factors in the kidney tissue of female rats following eight weeks of resistance training. Methods: Twenty-one female Wistar rats weighing 200 ± 20 g, aged eight weeks, were prepared from the Iran Pasture Institute. Following a week for acclimatization, the rats were randomly divided into three groups: control (n = 7), training + placebo (n = 6), and training + testosterone enanthate (n = 8). Resistance training included five days a week of climbing a 1-meter ladder with 26 stairs while bearing weights and two days of rest. In the first week, the weights were equal to 40% of the rats’ body weight. In the following weeks, the weight was increased by 20% per week. The rats were weighed two times a week. In the testosterone group, the rats were injected with 20 mg of testosterone enanthate thrice a week. Forty-eight hours following the last training session and testosterone injection, kidney tissue samples were collected to determine the gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) using real-time PCR. Results: The results showed that testosterone consumption significantly increased the gene expression of TNF-α and IL-6 in female rats undergoing resistance training (P = 0.001). Conclusions: The findings of this study demonstrated that using testosterone increased inflammatory factors in the kidney tissue of all female Wistar rats.

Decursinol angelate attenuates lipopolysaccharide induced acute lung injury by regulating AKT/NF κB pathway

Purpose: To investigate the effect of decursinol angelate in acute lung injury induced by lipopolysaccharide treatment.&#x0D; Methods: Human bronchial epithelial cells (BEAS-2B cells) and human pulmonary artery endothelial cells (HPAECs) were exposed to lipopolysaccharide to induce cell injury and then treated with 20, 40, or 60 μM decursinol angelate. Cell viability was quantified using a cell counting assay, while cell apoptosis was evaluated by western blot and flow cytometry. Colorimetric and enzyme-linked immunosorbent assay (ELISA) was used to measure oxidative stress. Expressions of tumor necrosis factor-alpha (TNF-α), interleukin-1β, and interleukin-6 were evaluated using quantitative real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Phosphorylation levels of p65, IκBα, AKT, and phosphatidylinositol 3-kinase were assessed by western blot, while the entry of p65 into the nucleus was investigated by indirect immunofluorescence assay.&#x0D; Results: Treatment with 40 or 60 μM decursinol angelate increased cell viability after lipopolysaccharide-induced damage. B-cell lymphoma 2 (Bcl2) and Bax expression were regulated, and the rate of apoptosis was inhibited. The concentration of superoxide dismutase and glutathione was elevated, and the density of malondialdehyde and myeloperoxidase decreased significantly. Inflammation was also suppressed by decursinol angelate by regulating TNF-α, interleukin-1β, and interleukin-6 expressions. Furthermore, decursinol angelate significantly decreased the phosphorylation of p65, IκBα, AKT, and phosphatidylinositol 3-kinase. Finally, decursinol angelate inhibited p65 entry into the cell nucleus.&#x0D; Conclusion: Decursinol angelate alleviates cell damage and apoptosis, reduces oxidative stress, and attenuates inflammation after lipopolysaccharide-induced acute lung injury by inhibiting AKT/NF-κB signaling pathway. Thus, decursinol angelate is a potential candidate for the treatment of lung injury.

Placental damage comparison between preeclampsia with COVID-19, COVID-19, and preeclampsia: analysis of caspase-3, caspase-1, and tumor necrosis factor-alpha expression

Some studies have reported that preeclampsia with coronavirus disease 2019 (COVID-19) significantly increases the risk of adverse perinatal outcome until near to three-fold over the normal pregnancy. Preeclampsia pathophysiology in theory, increases the perinatal mortality and morbidity starting from placental injury which is also believed to share the common pathway with COVID-19 infection. Major typical placental injuries for these matters could be apoptotic, necrotic, or pyroptotic. This study aimed to compare placental damage between those three conditions above in those three typical injuries. This was an observational analytic study with cross-sectional setting. Seventy-two pregnant women admitted to hospital consecutively with diagnosis of preeclampsia with COVID-19, Preeclampsia only and COVID-19 only. Diagnosis for preeclampsia was following FIGO criteria with at least one of the severe features. COVID-19 eligible for this study was PCR test confirmative with moderate to severe clinical degree. Placenta were taken after the delivery, and parameters were quantified with immunohistochemistry test for caspase-3, caspase-1, and TNF-alpha representing apoptotic, pyroptotic, and necrotic pathway respectively. Pregnancy with double complications, preeclampsia, and COVID-19, significantly has the highest placental damage on apoptotic, pyroptotic, and necrotic pathway shown from the caspase-3, caspase-1, and TNF-alpha expression in placenta (p <0.05). Moderate to severe degree of COVID-19 resulting higher placental damage compared to preeclampsia in all the three forms (p <0.05). Apoptotic process was the most prominent among other pathways. Preeclampsia with COVID-19 infection showed significant placental damage, with major changes related were apoptosis, inflammation, and necrosis. This data support poor perinatal outcome of pregnancy having preeclampsia and COVID-19 at the same time.

Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway.

We investigated the effects of lifelong aerobic exercise and 8months of detraining after 10months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.

Impact of heat stress length and dietary antioxidant supplementation on the nutrient digestibility, metabolism and immune response of fattening pigs

Study aimed to investigate the impact of long-term high ambient temperature (HAT) exposure and dietary antioxidant supplementation (elevated levels and in combination) on nutrient digestibility, metabolism and immune response of pigs. A total of 36 Danbred barrows (65.1 ± 2.81 kg) were allotted to four treatments: Trm1: HAT (28.9 ± 0.9 °C) + control diet (CD); Trm2: HAT + elevated vitamin C and E and Se and Zn; Trm3: HAT + further elevated vitamin C and E and Se and Zn; and Trm4: thermo-neutral ambient temperature (19.5 ± 0.9 °C) + CD. Nutrients (DM, CP, Cfat, CF, CA, GE) and minerals (Ca, P, Na, Zn, Se) digestibility were determined. Plasma metabolite and cytokine concentrations were investigated from the blood samples collected on d 15 and 28. Heat shock proteins (HSP 70 and 90) and tumor necrosis factor-alpha (TNF-α) expressions were investigated from jejunum samples of pigs. HAT did not significantly affect pigs' nutrient digestibility and retention (P > 0.05). However, Trm2 pigs had greater digestibility in terms of DM, CF, Ca, Zn, Se and retention of Ca, Zn, Na, and Se than Trm1 and Trm4 groups. Trm3 pigs had significantly higher (P < 0.05) creatinine concentrations than Trm4 pigs. HAT did not significantly affect the expression of cytokines; however, vitamins and micro-minerals supplementation in the diet significantly (P < 0.05) improved interleukin (IL) 10 expression, reduced TNF-α, and HSP70 expressions. Vitamin and micro-mineral fortified diet can improve pigs' nutrient and mineral digestibility and could alleviate inflammatory response in pigs exposed to HAT.

Thiolated chitosan hydrogel-embedded niosomes: A promising crocin delivery system toward the management of aphthous stomatitis

Aphthous stomatitis is a common inflammatory oral disease with challenging management. Crocin is a natural carotenoid that has shown great anti-inflammatory properties. The aim of this study was to develop thiolated chitosan (TCS)-based hydrogels containing niosomes to serve as a mucoadhesive crocin delivery system for aphthous stomatitis. Crocin-loaded niosomes were prepared and the impact of surfactant type, cholesterol content, and lipid to drug ratio on the characteristics of niosomes was evaluated. TCS was synthesized and the success of thiolation was investigated. The optimum niosomal formulation was loaded into the hydrogel and the hybrid system was characterized regarding the morphology, mucoadhesive properties, viscosity, chemical structure, in vitro drug release, and in vivo efficacy. The optimized niosome formulation showed 77% crocin entrapment, a particle diameter of 59 nm, and a zeta potential of −18 mV. The niosome-containing hydrogel exhibited pseudoplastic rheological behavior, mucoadhesive properties, suitable swelling, and sustained release of crocin. In vivo study revealed that the niosome-containing hydrogel improved ulcer healing and decreased the expression of tumor necrosis factor-alpha (TNF-α) and p53 while increasing the expression of vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Collectively, TCS hydrogel-embedded crocin-loaded niosomes is a promising therapeutic option for aphthous stomatitis. Chemical compounds studied in this articleCrocin (PubChem CID: 5281233)Chitosan (PubChem CID: 71853)Thioglycolic acid (PubChem CID: 1133)1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (PubChem CID: 2723939)5,5′-dithiobis (2-nitrobenzoic acid) (PubChem CID: 6254)Cholesterol (PubChem CID: 5997)

Silibinin Alleviates Lipopolysaccharide Induced Inflammation in Porcine Mammary Epithelial Cells via mTOR/NF-κB Signaling Pathway.

Inflammatory responses reduce milk production in lactating sow. Silymarin (Silibinin is main component) reduces the inflammatory reaction and increases milk yield in lactating sow in the previous study. In the present study, silibinin may be a previously unrecognized nutrients in inflammatory resolution in porcine mammary epithelial cells (PMECs) is hypothesized. PMECs are treated with or without lipopolysaccharide (LPS) in the absence or presence of silibinin to test cell viability, cell cycle, cell apoptosis, cellular inflammatory factors, and signaling protein phosphorylation and expression. Silibinin promotes the proliferation of PMEC independent of the estrogen pathway. In LPS-induced damage of PMECs, silibinin protects cell proliferation, as well as reduced cell apoptosis. Silibinin reverses the LPS-induced increase in tumor necrosis factor-alpha (TNF-α) expression compared with control. In addition, silibinin accentuates the LPS-induced decrease in the key proteins phosphorylated-ribosomal protein S6 (p-S6) and phosphorylated-mammalian target of rapamycin (p-mTOR) of the mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, silibinin reverses the increase in phosphorylated-nuclear factor-kappa B p65 (p-NF-κB p65), phosphorylated-Ikappab-alpha (p-IκB-α), and phosphorylated-Mitogen-activated protein kinase p38 (p-MAPK p38) expression in LPS-induced damage in PMECs. This study highlights silibinin-mTOR/NF-κB axis plays an important role in the control of inflammation in PMECs, and suggests that silibinin may be an effective dietary strategy to alleviate the inflammatory response in lactating sow.

Acetic acid-induced colitis modulating potential of total crude alkaloidal extract of Picralima nitida seeds in rats.

The total crude alkaloidal extract of Picralima nitida seeds (PNE) is known to possess anti-inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti-colitis potential of PNE using acetic acid-induced colitis model in rats. Sprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon. Treatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor-alpha, interleukin-1β, and p38 mitogen-activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production. It can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis.

Protective effects of methylsulfonylmethane (MSM) on barrier function injury of porcine intestinal epithelial cells (IPEC-J2) induced by lipopolysaccharide (LPS)

Methylsulfonylmethane (MSM) is a natural organic sulfur component that has anti-inflammatory and antioxidant properties. In this study, injury of porcine intestinal epithelial cell (IPEC-J2) models were used to investigate the effect of MSM on lipopolysaccharide (LPS)-induced porcine intestinal epithelium barrier damage. The results of the cell cycle showed that the cells in the G2/M phase decreased significantly with the supplementation of 300 mmol/L MSM ( P &lt; 0.05). The ELISA assay revealed that MSM could significantly inhibit the expression of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 ( P &lt; 0.01). Meanwhile, MSM could significantly increase the value of cell monolayer transepithelial electrical resistance while reducing the FITC-dextran flux permeability and lactate dehydrogenase activity in IPEC-J2 cells ( P &lt; 0.01). Additionally, 300 mmol/L MSM significantly increased both mRNA and protein expression of occludin, claudin-1, and ZO-1 ( P &lt; 0.05). Furthermore, MSM prevented the downregulation of epidermal growth factor receptor (EGFR) by LPS, indicating that MSM might enhance tight junction function through mechanisms of activation of EGFR-mediated protein synthesis in IPEC-J2 cells. Therefore, our findings suggested that MSM has protective effects on inflammation and epithelial barrier injury in LPS-induced IPEC-J2 cells, indicating that MSM might be used as a potential therapeutic agent in the pig industry.

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice.

Microglia-associated neuroinflammation plays a crucial role in the initiation and development of neuropathic pain (NeuP). AdipoRon is an analog of adiponectin that exerts an anti-inflammatory effect in various diseases through the adiponectin receptor 1 (AdipoR1) signaling mechanism. Adenosine monophosphate-activated protein kinase (AMPK) is a downstream target of AdipoR1, and the AdipoR1/AMPK pathway is involved in the regulation of inflammation. This study is aimed at investigating whether AdipoRon could alleviate NeuP by inhibiting the expression of microglia-derived tumor necrosis factor-alpha (TNF-α) through the AdipoR1/AMPK pathway. In vivo, the NeuP model was established in mice through the spared nerve injury. The von Frey test was used to detect the effect of AdipoRon on the mechanical paw withdrawal threshold. Western Blot was performed to detect the effects of AdipoRon on the expression of TNF-α, AdipoR1, AMPK, and p-AMPK. Immunofluorescence was performed to observe the effects of AdipoRon on spinal microglia. In vitro, lipopolysaccharide (LPS) was used to induce inflammatory responses in BV2 cells. The effect of AdipoRon on cell proliferation was detected by CCK-8. qPCR was used to examine the effects of AdipoRon on the expression of TNF-α and polarization markers. And the effect of AdipoRon on the AdipoR1/AMPK pathway was confirmed by Western Blot. Intraperitoneal injection of AdipoRon alleviated mechanical nociception in SNI mice, and the application of AdipoRon reduced the expression of TNF-α and the number of microglia in the ipsilateral spinal cord. Additionally, AdipoRon decreased the protein level of AdipoR1 and increased the protein level of p-AMPK in the ipsilateral spinal cord. In vitro, AdipoRon inhibited BV2 cell proliferation and reversed LPS-induced TNF-α expression and polarization imbalance. Furthermore, AdipoRon reversed the LPS-induced increase in AdipoR1 expression and decrease in p-AMPK expression in BV2 cells. AdipoRon may alleviate NeuP by reducing microglia-derived TNF-α through the AdipoR1/AMPK pathway.

Intraperitoneal injection of β-glucan during the suckling period improved the intestinal health of newly weaned rabbits by enhancing immune responses

The newly weaned rabbits are susceptible to unpredictable pathogens, which often lead to diarrhea. Recent studies have confirmed that innate immunity can also be trained. An essential feature of trained immunity is a faster and stronger immune response to both homologous and heterologous reinfections. Therefore, the present study investigated the effect of intraperitoneal injection of β-glucan during the suckling period on protecting weaned rabbits from diarrhea and its mechanism. Sixty-four suckling rabbits were randomly divided into two groups based on litter and weight: the control group (C) and the trained group (T). At 6 and 4 days before weaning, rabbits in the two groups were intraperitoneally injected with physiological saline solution (PSS) and β-glucan dissolved in PSS, respectively, and 10 in each group were randomly selected two weeks after weaning for sampling. Results showed that the diarrhea rate and the crypt depth of the ileum in the trained group were decreased (P < 0.05 or P < 0.01). Compared with the control group, rabbits receiving β-glucan during suckling exhibited an increase in the gene expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) (P < 0.01) and a decrease in that of interleukin-6 (IL-6) (P < 0.05). Pre-stimulation with β-glucan also increased the concentration of serum immunoglobin A (IgA) and immunoglobin G (IgG) (P < 0.05) and that of ileal secretory immunoglobulin (sIgA) and lysozyme (LYZ) (P < 0.05) after weaning. In addition, the trained rabbits showed lower serum malondialdehyde (MDA) and hydroxyl radical levels (P < 0.001). Notably, the microbial communities of ileum mucus in the trained group showed more homogeneity and aggregation. Our results confirmed that pre-stimulation with β-glucan before weaning improved intestinal health by enhancing the immunity ability of both innate and adaptive immune in the newly weaned rabbits, providing an experimental and theoretical basis for the use of β-glucan-induced trained immunity in preventing intestinal infection after weaning in rabbits.

The Potential Protective Eff ects of Pirfenidone on Diclofenac Sodium Induced Gastric Ulcer in a Rat Model

Introduction: Non-steroidal anti-infl ammatory drugs (NSAIDs), are widely prescribed in clinical practice because of their ability to reduce pain, fever, and infl ammation. However, NSAID-induced gastric mucosal damage is the major side eff ect of these medications. This study aims to reduce gastric mucosal lesions caused by NSAIDs by using pirfenidone by investigating their eff ect on histological, gastric gross mucosal damage. Method: 30 healthy male albino rats were divided into 3 groups each of ten (N=10). A single oral dose of diclofenac sodium (150 mg/kg body weight) was used to induce ulceration for all groups except fi rst. The vehicle (tween 80+NS) was given to the fi rst group, while diclofenac sodium was given to the second group and to all pre-treated groups. The third group were pre-treated with pirfenidone (300 mg/kg). At the end of the experiment, histological examination, and antioxidant and antiinfl ammatory parameters by immunohistochemistry method were evaluated. Results: Diclofenac sodium at a dose (150 mg/kg) produces a signifi cant increment (p &gt; 0.01) in gastric damage score, the expression of tumor necrosis factor-alpha (TNF-α), myeloperoxidase, malonaldehyde, and the ulcer formation percent, compared to the healthy rat’s group. Pirfenidone at a dose of (300 mg/kg) pretreatment in diclofenac induced-ulcer in rats produces a signifi cant reduction (p &gt; 0.01) in gastric damage score, the expression of TNF-alpha, myeloperoxidase, the expression of TNF-alpha, myeloperoxidase, malonaldehyde, and in the ulcer formation percent, yet, less eff ectively than omeprazole and pirfenidone. Conclusion: Diclofenac can be reduced or prevented by the pretreatment of pirfenidone. Pirfenidone showed similar results to the standard treatment (Omeprazole), the protective eff ect of pirfenidone was mainly through their antioxidant and anti-infl ammatory activity by reducing oxidation markers like MPO and MDA, and also reducing infl ammatory cytokines like TNF-alpha

Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNFα/NLRP3/Caspase-1/IL-1β pathway and macrophage M1 polarization

As a chronic inflammatory bowel disease, ulcerative colitis (UC) imposes a significant burden on public healthcare worldwide due to its increasing morbidity. Chinese medicines are regarded as potent therapeutic agents for UC treatment with minimal side effects. In the present study, we sought to determine the novel role of a traditional medicine Qingre Xingyu (QRXY) recipe in the development of UC and aimed to contribute to the currently available knowledge about UC by exploring the downstream mechanism of QRXY recipe in UC. Mouse models of UC were established by injections with dextran sulphate sodium (DSS), where the expression of tumor necrosis factor-alpha (TNFα), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β) was determined followed by an analysis of their interactions. The DSS-treated NLRP3 knockout (−/−) Caco-2 cell model was successfully constructed. The in vitro and in vivo effects of the QRXY recipe on UC were investigated with the determination of disease activity index (DAI), histopathological scores, transepithelial electrical resistance, FITC-dextran, as well as cell proliferation and apoptosis. In vivo and in vitro experiments indicated that the QRXY recipe reduced the degree of intestinal mucosal injury of UC mice and functional damage of DSS-induced Caco-2 cells by inhibition of the TNFα/NLRP3/caspase-1/IL-1β pathway and M1 polarization of macrophages, and TNFα overexpression or NLRP3 knockdown could counterweigh the therapeutic effects of QRXY recipe. To conclude, our study elicited that QRXY inhibited the expression of TNFα and inactivated the NLRP3/Caspase-1/IL-1β pathway, thereby alleviating intestinal mucosal injury and relieving UC in mice.

Finding Molecular Inhibitors of the Inflammatory Pathway in the Large Intestine Along with Molecular Dynamics with Emphasis on the Use of TCM Database

Background: Due to the fact that colon inflammation is one of the most common diseases in the country, the interest in using herbal medicines to cure intestinal inflammation is increasing day by day. Objectives: In the present research, we aimed to identify the target molecules in the immune system by analyzing the transcriptome of these diseases and using the virtual screening technique to search for plant compounds that have antagonistic capabilities for these receptors. Also, by using this in vitro culture, check and confirm the anti-inflammatory properties of these compounds. Methods: The population study includes 200 human transcriptome runs, about 60 thousand compounds related to medicinal plants, and in vitro experiments with at least three experimental replicates and three technical replicates. In this study, the anticancer and immunomodulatory effects of aqueous extracts of rosemary and nettle medicinal plants were investigated as a promising source of cancer treatment against the AGS cell line derived from gastric cancer (AGS-Cell-DGC). IC50 of the extracts was determined by MTT assay. Flow cytometry and real-time PCR (RT-PCR) were measured. Results: The MTT test on the survival percentage of AGS cell line (90%) derived from gastric cancer showed that the highest amount of live cells was observed in control, and the lowest amount was observed in the simultaneous combination of rosemary and nettle extract and then nettle (100%). The highest expression of interleukin 1-beta (IL-1β) gene occurred in the control, and the lowest expression occurred in the simultaneous combination of nettle and rosemary extracts. The highest expression of tumor necrosis factor-alpha (TNF-α) gene occurred in the control, and the lowest expression occurred in the simultaneous combination of nettle and rosemary extracts. Conclusions: The results showed that the highest amount of live cells was observed in the control, and the lowest amount was observed in the simultaneous combination of rosemary and nettle extract and then nettle (100%) alone. However, further clinical trials are needed to confirm the results of this research.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes

Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

P031 CKD-506, a new histone deacetylase 6 inhibitor, suppresses immune cells and restores intestinal epithelial function

Abstract Background Inflammatory bowel disease (IBD) represents a group of chronic immune-mediated diseases of the gastrointestinal tract, characterized by recurrent inflammation and consequential damage of the gastrointestinal tract. Histone deacetylases (HDACs) are a family of mostly ubiquitous enzymes that remove acetyl groups from lysines on histone proteins to regulate gene transcription. HDAC6, which is localized to the cytoplasm, appears to be a promising candidate in IBD treatment. The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 (HDAC6) inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function. Methods Lipopolysaccharide (LPS)-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor-alpha (TNF-α) expression was measured using enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, with examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription PCR, immunofluorescence, and FITC-dextran permeability assay. Results TNF-α secretion, a pivotal pro-inflammatory mediator in IBD, of LPS-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction of barrier permeability in a dose-dependent manner. Conclusion The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4+ T cells and improved gut barrier function, indicating its potential as a promising and competent candidate for small-molecule medicine for IBD treatment.

Ameliorative Potential of Betanin on Cigarette Smoke Extract-induced Respiratory Mucosal Inflammation and Oxidative Stress in the Adult Zebrafish Model

Background Betanin, a natural pigment and glycosidic bioactive compound, possesses anti-inflammatory antioxidant activity. Objectives In this study, we evaluated the potential effect of betanin on cigarette smoke extract (CSE)-induced pulmonary inflammation in the zebrafish model. Materials and Methods Zebrafish were randomly divided into five groups with control, CSE-exposed and betanin-treated after CSE exposure for 3 and 6 days. Oxidative stress-related parameters like reactive oxygen species (ROS), nitric oxide (NO) and myeloperoxidase (MPO) were analysed, histopathological studies were carried out and gene expression of proinflammatory tumour necrosis factor-alpha, inducible NO synthase and anti-inflammatory interleukin-10 cytokines was determined. Results Treatment with betanin reduced ROS, MPO and NO with histopathological improvement, alleviating CSE-induced pulmonary inflammation. Further, decreased expression of the proinflammatory gene and increased expression of the anti-inflammatory gene were observed after 6 days of treatment. Conclusion Betanin exhibits a protective effect against CSE exposure by inhibiting oxidative stress and inflammation.