Tumor Necrosis Factor-α Expression Research Articles

Anti-inflammation and gut microbiota regulation properties of fatty acids derived from fermented milk in mice with dextran sulfate sodium-induced colitis.

The by-products of milk fermentation by lactic acid bacteria provide potential health benefits to the balance of host intestinal microflora. In this study, the anti-inflammatory properties of fatty acids from monoculture-strain (Lactiplantibacillusplantarum A3) and multiple-strain (Streptococcus thermophilus, Lactobacillus bulgaricus, and L. plantarum A3 1:1:2) fermented milk were evaluated in a mouse model of dextran sulfate sodium-induced colitis, and the gut microbiota regulation properties of the fatty acids were also investigated. Results showed that fatty acids can attenuate the inflammatory response by inhibiting the expression of inflammatory factors IL-6 and tumor necrosis factor-α, and blocking the phosphorylation of the JNK in MAPK signal pathway. In addition, the relative abundance of the taxa Akkermansia and Lactobacillus were both enriched after the fatty acid intervention. This finding suggests that fatty acids from the milk fermentation with mixed lactic acid bacteria starters can reduce the severity of dextran sulfate sodium-induced colitis and enhance the abundance of the probiotics in the mice intestinal tract.

Polysaccharide extracted from Morchella esculenta inhibits carrageenan-induced thrombosis in mice

MCP prevented carrageenan-induced thrombosis in mice by reducing platelets activation, oxidative stress and monocytes adhesion to damaged endothelial cells. MCP has great potential to develop into a natural antithrombotic drug. Our study suggests a new application of Morchella esculenta , which can be used as food supplements and nutraceuticals to benefit human health. • Morchella esculenta Polysaccharide reduces thrombi formed in in mouse tissues. • Morchella esculenta Polysaccharide attenuates platelet activation. • Morchella esculenta Polysaccharide inhibits oxidative stress in platelets and endothelium cells. • Morchella esculenta Polysaccharide inhibits adhesion of monocytes to endothelium cells. Thrombosis is one of the leading causes of death worldwide and is associated with inflammation and oxidative stress. This study aims to investigate the effect of Morchella esculenta Polysaccharide (MCP) on thrombosis. Our results showed that MCP inhibited thrombi in blood vessels of mouse tail, liver and lung, which was contributed by the inhibition of collagen accumulation, tumor necrosis factor-α and P-selectin expression. In vitro , human platelet clot retraction test indicated that MCP inhibited platelet activation, which was related to inhibition of platelet receptors, AKT and ERK1/2 pathways. Additionally, MCP inhibited oxidative stress by inducing anti-oxidative enzymes in human platelets and human umbilical vein vascular endothelium cells (HUVECs). Moreover, MCP inhibited oxidized low-density lipoprotein or LPS-induced adhesion of monocytes to HUVECs by reducing adhesion molecules expression. Taken together, these data demonstrate MCP exhibits antithrombotic properties, indicating Morchella esculenta can be used as food supplements and nutraceuticals against thrombosis.

Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.).

Inflammation is important in the pathogenesis of several chronic diseases. The anti-inflammatory properties of berries have been investigated but the anti-inflammatory activity of bilberry has received little attention and a detailed review is yet to be published. Therefore, we compiled information on the phytochemicals of bilberry and preclinical and clinical studies of its anti-inflammatory properties. The review was based on studies from 2007 to date. Phytoconstituents of bilberries were phenolic acids, organic acids, anthocyanins, coumarins, flavonols, flavanols, tannins, terpenoids, and volatile chemicals. Data from cell and animal model studies show that bilberry has an anti-inflammatory effect by lowering tumor necrosis factor-α, interleukin (IL)-6, and IL-1β expression, inducing nitric oxide synthases and cyclooxygenases, and altering the nuclear factor kappa B and Janus kinase-signal transducer and activator of transcription signaling pathways. Bilberry supplementation as fruits (frozen, processed, and whole), juices, and anthocyanins reduced levels of inflammatory markers in most clinical studies of metabolic disorders. Therefore, bilberry may be useful for the prevention and treatment of chronic inflammatory disorders.

Decreased frequency of a novel T-lymphocyte subset, CD3+ CD4- CD7+ CD57- T cells, in hepatitis B virus-related end-stage liver disease might contribute to disease progression.

CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator(BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.

Anti-inflammatory effects of β-ionone-curcumin hybrid derivatives against ulcerative colitis

A series of β-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological characteristics of two parent molecules and to obtain a leading compound with higher biological activity. Through the initial screening, the structure activity relationship of their hybrid derivatives as inhibitors of nitric oxide (NO) production showed that meta-substituted derivatives exhibited the best inhibitory activity, among which 1h was the best one. In lipopolysaccharide-induced Raw264.7 macrophage cells, 1h showed anti-inflammatory activity by inhibiting the productions of NO and reactive oxygen species, the expressions of Interleukin-1β and tumor necrosis factor-α, and the translocation of nuclear factor (NF)-κB from the cytosol to the nucleus. Furthermore, molecular docking simulation displayed that 1h could interact with cluster of differentiation 14 to inhibit the toll-like receptor 4/NF-κB signaling. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) of mice, 100 mg/kg of 1h could significantly reduce the colon length shortening and protect against colon injury, liver injury and oxidative stress in DSS-induced UC of mice. Besides, 1h was safety in vivo. In conclusion, 1h was the potential anti-inflammatory agent, and further investigations were underway in our laboratory.

Estimation of Metabolic Effects upon Cadmium Exposure during Pregnancy Using Tensor Decomposition.

A simple tensor decomposition model was applied to the liver transcriptome analysis data to elucidate the cause of cadmium-induced gene overexpression. In addition, we estimated the mechanism by which prenatal Cd exposure disrupts insulin metabolism in offspring. Numerous studies have reported on the toxicity of Cd. A liver transcriptome analysis revealed that Cd toxicity induces intracellular oxidative stress and mitochondrial dysfunction via changes in gene expression, which in turn induces endoplasmic reticulum-associated degradation via abnormal protein folding. However, the specific mechanisms underlying these effects remain unknown. In this study, we found that Cd-induced endoplasmic reticulum stress may promote increased expression of tumor necrosis factor- (TNF-). Based on the high expression of genes involved in the production of sphingolipids, it was also found that the accumulation of ceramide may induce intracellular oxidative stress through the overproduction of reactive oxygen species. In addition, the high expression of a set of genes involved in the electron transfer system may contribute to oxidative stress. These findings allowed us to identify the mechanisms by which intracellular oxidative stress leads to the phosphorylation of insulin receptor substrate 1, which plays a significant role in the insulin signaling pathway.

Icing after skeletal muscle injury decreases M1 macrophage accumulation and TNF-α expression during the early phase of muscle regeneration in rats.

Following skeletal muscle injury, both myogenic and immune cells interact closely during the regenerative process. Although icing is still a common acute treatment for sports-related skeletal muscle injuries, icing after muscle injury has been shown to disrupt macrophage accumulation and impair muscle regeneration in animal models. However, it remains unknown whether icing shortly after injury affects macrophage-related phenomena during the early stages of muscle regeneration. Therefore, we focused on the distribution of M1/M2 macrophages and cytokines expressed predominantly by macrophages during the early stages of muscle regeneration after muscle crush injury. Icing resulted in a decrease, not retardation, in the accumulation of M1 macrophages, but not M2 macrophages, in injured muscles. Consistent with the decrease in M1 macrophage accumulation, icing led to a reduction, instead of delay, in the level of tumor necrosis factor-α (TNF-α) expression. Additionally, at subsequent timepoints, icing decreased the number of myogenic precursor cells in the regenerating area and the size of centrally nucleated regenerating myofibers. Together, our findings suggest that icing after acute muscle damage by crushing disturbs muscle regeneration through hindering tM1 macrophage-related phenomena.

Comparison of growth, and non-specific immune of crisp and ordinary tilapia (Oreochromis niloticus)

Tilapia (Oreochromis niloticus) is a kind of worldwide farmed fish that is commercially cultured in more than a hundred nations. The tilapia dietary faba bean (Vicia faba L.) for 90– 120 d improves muscle quality such as higher muscle hardness and crispiness. However, faba bean contain a wide variety of antinutritional factors such as phenolics, tannins, trypsin inhibitor activity, and phytic acid. Antinutritional factors through themselves or their metabolic products affect the health of fish. This study was compared growth, antioxidant activity, carbon metabolic enzyme activity and immune-related gene expression profiles between the ordinary and crisp tilapia. The results indicated that crisp tilapia (888.00 ± 200.83 g) had a significantly lower body weight compared with ordinary tilapia (1078.67 ± 162.56 g) (P < 0.05). There were no significant differences in superoxide dismutase (SOD) and antioxidant capacity (T-AOC) between crisp and ordinary tilapia in both serum and liver. The crisp tilapia recorded significantly lower acid phosphatase (ACP), and alkaline phosphatase (AKP) in contrast to the ordinary tilapia in serum (P < 0.05), but not significant in liver. The crisp tilapia (serum: 8.05 ± 1.23 U/mL, liver: 7.59 ± 1.09 U/mL) exposure could significantly inhibit glucose 6-phosphate dehydrogenase (G6PD) activities compared with ordinary tilapia (serum: 5.07 ± 0.91 U/mL, liver: 4.10 ± 1.18 U/mL) (P < 0.05). The lysozyme (LZM) and triglyceride (TG) of ordinary and crisp tilapia were similar. The heat shock protein70 (Hsp70) and tumor necrosis factor-α (TNF-α) expression of crisp tilapia demonstrated significant upregulation when compared with ordinary tilapia in the haemocytes and liver, whereas the interleukin-1β (IL-1β), metallothionein (MT), and chemokine C-C-Motif Ligand 3 (CCL) expression of crisp tilapia were significantly deregulated in the liver. In conclusion, the crisp tilapia can decrease growth, ACP, AKP, and G6PDH activity, whereas Hsp70 and TNF-α expression of crisps demonstrated significant upregulation. The results would contribute to comprehend the physiological parameters during tilapia crisping process and exploring the mechanism of tilapia brittleness.

Possible effects of clinoptilolite on small intestinal ischemia-reperfusion injury caused by experimental mesenteric artery occlusion

Abstract Objectives Mesenteric ischemia is a surgical emergency caused by poor blood supply to the intestines. In ischemia, the decrease in blood flow to the tissue causes acidosis and cell death through anaerobic metabolism. Clinoptilolite is one of the most abundant natural zeolites, and it is used for its ion exchange and adsorbent properties. Clinoptilolite has been reported to have an immune-enhancing, anti-carcinogenic, and antioxidant effect in-vitro/in-vivo studies. Clinoptilolite’s histological and biochemical effects on ischemic small intestines. Methods The experimental animals were randomly divided into sham, control, and clinoptilolite treatment group. Clinoptilolite was administered intraperitoneally after ischemia/reperfusion. Cardiac blood was stored for biochemical analysis. Total antioxidant levels and total oxidant levels were analyzed from the sera taken from groups. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expressions in blood samples were determined by RT-qPCR. At the end of the reperfusion, terminal ileum tissues were taken for histological tests. Results The mean TNF-α expression level was 3.89 in the control group and 2.91 in the clinoptilolite treatment group. The mean IL-6 expression levels were 2.32 in the control group and 1.49 in the clinoptilolite treatment group. Conclusions clinoptilolite administration provided healing in the rat ischemia-reperfusion injury model.

Differential recruitment of monocyte-derived macrophages in control and stellate cell-depleted mice during recurrent carbon tetrachloride-induced acute liver injury.

Liver depleted of hepatic stellate cells (HSCs) is resistant to ischemia/reperfusion-, concanavalin A-, and acetaminophen-induced acute injury. Whether HSCs regulate carbon tetrachloride (CCl4 )-induced acute liver injury is not known. CCl4 treatment damages pericentral hepatocytes that express CCl4 -metabolizing Cyp2E1 and activates HSCs. We investigated whether HSC-depletion in mice transgenic for thymidine kinase under the glial fibrillary acidic protein promoter (GFAP-TK-Tg) confers resistance to injury and inflammation due to CCl4 rechallenge. GFAP-TK-Tg or wild type (WT) mice were administered 0.16 ml/kg CCl4 (3× at 3 days intervals), then 40 μg/g/day ganciclovir for 10 days. The treatment depletes ~70%-75% HSCs from GFAP-TK-Tg but not WT mice while the liver recovers from earlier CCl4 -induced injury. Mice were then administered CCl4 , and liver injury and inflammation were determined at 24 h. HSC-depleted and HSC-sufficient mice showed similar CCl4 -induced hepatocyte necrosis and oxidative stress. However, increase in F4/80+ macrophages, but not CD68+ cells, was greater in CCl4 rechallenged HSC-depleted compared to HSC-sufficient mice. Expression of tumor necrosis factor-α (TNF-α), CCL2, and CXCL1 increased similarly, whereas increase in interleukin-6 (IL6), IL1β, and IL10 expression was higher in CCl4 rechallenged HSC-depleted compared to HSC-sufficient mice. CCl4 rechallenge of HSC-sufficient mice rapidly activated HSCs causing significant fibrosis with increased expression of Col1a1, transforming growth factor β1 (TGFβ1), tissue inhibitors of metalloproteinases 1 (TIMP1); increase in TIPM1 was much lower and metalloproteinases 13 (MMP13) greater in CCl4 rechallenged HSC-depleted mice. Interestingly, hepatic recruitment of both profibrogenic (Ly6Chi ) and antifibrogenic restorative (Ly6Clo ) macrophages, and neutrophils was significantly greater in CCl4 rechallenged HSC-depleted mice. These data suggest that CCl4 directly damages hepatocytes but HSCs regulate inflammation. Rapid fibrogenesis in CCl4 rechallenged HSC-sufficient mice recovered from earlier injury indicates that even transiently activated HSCs that had reverted to the quiescent phenotype remain primed to become reactivated.

PH-responsive theranostic nanoplatform of ferrite and ceria co-engineered nanoparticles for anti-inflammatory.

Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe3+-incorporated ceria-based MSN nanoparticles possessing a higher Ce3+-to-Ce4+ ratio than those revealed by ceria-only nanoparticles. The as-prepared Fe/Ce-MSN nanoparticles exhibited an excellent efficiency in scavenging reactive oxygen species (ROS), which is attributed to improving the superoxide dismutase (SOD) mimetics activity by increasing Ce3+ content and maintaining a higher activity of catalase (CAT) mimetics via including ferrite ion in nanoparticles. The fast Fe/Ce-MSN biodegradation, which is sensitive to the mild acidic microenvironment of inflammation, can accelerate Fe/Ce ion release, and the freed Fe ions enhanced T2-weighted magnetic resonance imaging in the inflammation site. PEGylated Fe/Ce-MSN nanoparticles in vitro cell models significantly attenuated ROS-induced inflammation, oxidative stress, and apoptosis in macrophages by scavenging overproduced intracellular ROS. More importantly, Fe/Ce-MSN-PEG NPs exhibited significant anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels in vitro. Additionally, it can promote the macrophages polarization of pro-inflammatory M1 phenotype towards an anti-inflammatory M2 phenotype. Thus, the novel pH-responsive theranostic nanoplatform shows great promise for inflammation and oxidative stress-associated disease treatment.

Dimethyl Fumarate (DMF) Alleviated Post-Operative (PO) Pain through the N-Methyl-d-Aspartate (NMDA) Receptors.

The management of post-operative (PO) pain has generally been shown to be inadequate; therefore, acquiring a novel understanding of PO pain mechanisms would increase the therapeutic options available. There is accumulating evidence to implicate N-methyl-d-aspartate (NMDA) receptors in the induction and maintenance of central sensitization during pain states by reinforcing glutamate sensory transmission. It is known that DMF protects from oxidative glutamate toxicity. Therefore, NMDA receptor antagonists have been implicated in peri-operative pain management. Recent advances demonstrated that dimethyl fumarate (DMF), a non-opioid and orally bioavailable drug, is able to resolve neuroinflammation through mechanisms that drive nociceptive hypersensitivity. Therefore, in this study, we evaluated the role of DMF on pain and neuroinflammation in a mouse model of PO pain. An incision of the hind paw was performed, and DMF at two different doses (30 and 100 mg/kg) was administered by oral gavage for five consecutive days. Mechanical allodynia, thermal hyperalgesia and locomotor dysfunction were evaluated daily for five days after surgery. Mice were sacrificed at day 7 following PO pain induction, and hind paw and lumbar spinal cord samples were collected for histological and molecular studies. DMF administration significantly reduced hyperalgesia and allodynia, alleviating motor disfunction. Treatment with DMF significantly reduced histological damage, counteracted mast cell activation and reduced the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) inflammatory pathway, in addition to downregulating tumor necrosis factor-α (TNF-α), Interleukin-1β (Il-1β) and Il-4 expression. Interestingly, DMF treatment lowered the activation of NMDA receptor subtypes (NR2B and NR1) and the NMDA-receptor-interacting PDZ proteins, including PSD93 and PSD95. Furthermore, DMF interfered with calcium ion release, modulating nociception. Thus, DMF administration modulated PO pain, managing NMDA signaling pathways. The results suggest that DMF positively modulated persistent nociception related to PO pain, through predominantly NMDA-receptor-operated calcium channels.

Neuroprotective effect of peanut against oxidative stress in streptozotocin-induced diabetic rats

ABSTRACT Diabetes mellitus is characterized by structural abnormalities, oxidative stress and neuroinflammation. This study aimed to determine the antioxidative therapeutic effects of peanut supplementation in improving brain damage resulted from streptozotocin (STZ)-induced diabetes. Forty male Wistar albino rats (Rattus novergicus) were categorized into four groups: control, peanut-supplemented, diabetic, diabetic and peanut-supplemented. The brain was dissected and subjected to biochemical analyses which indicated the role of diabetes in downregulating the expression of superoxide dismutase (SOD), dopamine (DA), serotonin (5-HT), adenosine triphosphate (ATP) and upregulating the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), 5-lipoxygenase (5-lOX), 8-hydroxy-deoxy guanosine (8-OHdG), Amyloid-β, α-amylase and tau protein expression levels. peanut treatment enhanced the diabetic-dependent brain histopathological features in the cerebrum and hippocampus, the immunohistochemical localization indicated significant downregulation at the expression of synaptophysin and caspase 3. Peanut supplementation significantly downregulated the gene expression of BAX, SOD, Myloperoxidase (MPO), Tumor necrosis factor- α (TNF-α), peroxisome proliferator-activated receptors (PPAR-α and PPAR-γ) and upregulated glial fibrillary acidic protein (GFAP) expression. In conclusion, peanut supplementation showed therapeutic potential against brain damage induced by diabetes. Peanut treatment significantly protected the brain from diabetic-related oxidative stress, and increased dopamine and serotonin levels by restoring the redox balance.

Relationship between mucosal TNF-α expression and Th1, Th17, Th22 and Treg responses in Helicobacter pylori infection

Helicobacter pylori (H. pylori)-induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori-associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells. Fifty-five patients with H. pylori-associated gastritis, 47 patients with H. pylori-associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments. Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group. These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study.

(4E)-7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (DPHB) derived from A. officinarum Hance has been reported to exert anti-inflammatory and anti-insulin resistance (IR) effects. We explored the molecular mechanism of DPHB ameliorating IR through network pharmacological prediction and in vitro analysis. The PI3K/AKT and TNF signaling pathways are the core pathways for DPHB to exert anti-IR, and the key proteins of this pathway were confirmed by molecular docking. In the IR-3T3-L1 adipocyte model, DPHB significantly promoted glucose uptake and the glucose transporter type 4 (GLUT4) translocation. In addition, DPHB significantly improved lipid accumulation, triglyceride content, and the mRNA expression of key adipokines [such as peroxisome proliferator-activated receptors-gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1)]. DPHB inhibited the protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and phosphorylated nuclear factor-κB (NF-kB), as well as promoted the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylated PI3K, and phosphorylated AKT. More interestingly, validation of the PI3K inhibitor LY294002 revealed that these changes were dependent on the activation of PI3K. Our cumulative findings thereby validate the potential of DPHB to alleviate and treat IR and the related diseases by regulating the PI3K/AKT and TNF-α signaling pathways.

Prophylactic Administration of Magnesium Oxide Prevents Dextran Sulfate Sodium-Induced Colonic Injury in Mice.

We previously demonstrated that per os administration and ad libitum ingestion of a magnesium chloride (MgCl2) solution had a prophylactic effect on dextran sulfate sodium (DSS)-induced colitis in mice, magnesium being considered to play a role in this preferable action. Magnesium oxide (MgO) is a commercially available magnesium formulation, but whether or not it prevents development of colitis is unknown. In this study, we investigated the effect of MgO administration on development of colitis in DSS-treated male C57BL/6J mice. Experimental colitis was induced by ad libitum ingestion of 1% (w/v) DSS, and the colitis severity was evaluated by disease activity index (DAI) scores, histological assessment and colonic expression of inflammatory cytokines. A 1 mg/mL MgO solution was administered to mice through ad libitum ingestion from a day before DSS treatment to the end of the experimental period of 12 d. In addition, the effects of DSS, MgO and their combination on the gut microbiota were investigated by 16S ribosomal RNA metagenome analysis. DSS-induced elevation of DAI scores was partially but significantly decreased by MgO administration, while MgO administration had no apparent effect on the shortened colonic length, elevated mRNA expression of colonic interleukin-1β and tumor necrosis factor-α, increased accumulation of colonic mast cells, or altered features of the gut microbiota in DSS-treated mice. Overall, we demonstrated that MgO had a prophylactic effect on the development of colitis in DSS-treated mice by preventing histological colonic damage, but not colonic inflammation or alteration of the gut microbiota.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUNDRadiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM).AIMTo explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODSWe used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed.RESULTSWMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1β, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid).CONCLUSIONWMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats.

The aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was conducted to evaluate the wound-healing process of Amitrip-NPs in streptozotocin-induced diabetic rats. Wound contraction was accelerated in rats treated with Amitrip-NPs. Histological examinations confirmed these findings, with expedited remodeling and collagen deposition in the NPs-treated animals. The formula showed anti-inflammatory activities as demonstrated by inhibition of interleukin-6 (IL-6) expression and tumor necrosis factor-α (TNF-α) expression, as well as enhanced expression of interleukin-10 (IL-10). In addition, Amitrip-NPs protected against malondialdehyde (MDA) buildup and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. The pro-collagen activity of Amitrip-NPs was confirmed by the observed enhancement of hydroxyproline wounded skin content, upregulation of Col 1A1 mRNA expression and immune expression of collagen type IV expression. Further, Amitrip-NPs significantly increased expression transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-B (PDGF-B) and cluster of differentiation 31 (CD31). In conclusion, the developed Amitrip-NPs expedited wound healing in diabetic rats. This involves anti-inflammatory, antioxidant, pro-collagen and angiogenic activities of the prepared NPs. This opens the gate for evaluating the usefulness of other structurally related tricyclic antidepressants in diabetic wounds.

Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice.

Loss of fertility is a major concern for female reproductive-age cancer survivors, since a common side-effect of conventional cytotoxic cancer therapies is permanent damage to the ovary. While immunotherapies are increasingly becoming a standard of care for many cancers-including in the curative setting-their impacts on ovarian function and fertility are unknown. We evaluated the effect of immune checkpoint inhibitors blocking programmed cell death protein ligand 1 and cytotoxic T lymphocyte-associated antigen 4 on the ovary using tumor-bearing and tumor-free mouse models. We find that immune checkpoint inhibition increases immune cell infiltration and tumor necrosis factor-α expression within the ovary, diminishes the ovarian follicular reserve and impairs the ability of oocytes to mature and ovulate. These data demonstrate that immune checkpoint inhibitors have the potential to impair both immediate and future fertility, and studies in women should be prioritized. Additionally, fertility preservation should be strongly considered for women receiving these immunotherapies, and preventative strategies should be investigated in future studies.

Myrrhone inhibits the progression of hepatic fibrosis by regulating the abnormal activation of hepatic stellate cells.

We focus on exploring the antihepatic fibrosis effect of Myrrhone (Myr), a compound extracted from myrrh, and its effective target. Mouse hepatic stellate cells (HSCs) were cultured in vitro and activated by transforming growth factor-β induction. After Myr intervention, cell viability was assessed by theCell Counting Kit-8 assay. The α-smooth muscle actin(α-SMA) and Collagen I levels were measured by immunofluorescence, and the expressions of tumor necrosis factor-α, interleukin-6, andmatrix metalloproteinase-9were examined by enzyme-linked immunosorbent assay, and the p-Smad3 protein level in HSCs was determined by Western Blot. Small molecule-protein docking and pull-down experiments were conducted to validate the binding capacity between Nard and Smad3. In animal experiments, a mouse model of hepatic fibrosis was established with carbon tetrachloride. Myr was administered by gavage daily to determine the serum alanine aminotransferase and aspartate transaminase levels. The severity of hepatic fibrosis was evaluated by Masson staining, the α-SMA and Collagen I expressions were measured by immunohistochemistry, and the histopathological changes were examined by Sirius red and hematoxylin and eosin staining. Myr suppressed the abnormal activation of HSCs, inhibited the cell viability, downregulated the α-SMA and Collagen I, and inhibited the p-Smad3 expression. After silencing Smad3, the effect of Myr was inhibited. Molecular docking and pull-down experiments revealed the presence of a targeted binding relationship between Myr and Smad3. In mouse experiments, Myr could inhibit hepatic fibrosis. This study discovers that Myr can affect the phosphorylation of Smad3, and inhibit the activation of HSCs and the progression of hepatic fibrosis.