Expression Levels Of Inflammatory Cytokines Research Articles

The occurrence and development of radiation-induced lung injury after interstitial brachytherapy and stereotactic radiotherapy in SD rats

BackgroundTo compare the severity of radiation-induced lung injury (RILI) after the right lung of SD rats received interstitial brachytherapy and stereotactic radiotherapy (SBRT).MethodsRILI rat model was established using interstitial brachytherapy and SBRT methods, respectively. CT scan was performed to analyze the lung volume and the CT value difference between the left and right lungs in rats. Then the lung tissues were analyzed through H&E staining, peripheral blood was extracted to detect the expression levels of serum inflammatory cytokines, pro-fibrotic cytokines, and fibrotic-inhibiting cytokines by ELISA.ResultsThe difference between right and left lung CT values was significantly elevated in the SBRT group when compared with the control group and the interstitial brachytherapy group (P < 0.05). The IFN-γ expression in the interstitial brachytherapy group was significantly different from that in the SBRT group at week 1, 4, 8 and 16. Besides, the expressions of IL-2, IL-6 and IL-10 in SBRT group were significantly higher than that of interstitial brachytherapy group (P < 0.05). The TGF-β expression in interstitial brachytherapy group reached its peak with the increase of time from week 1 to week 16, and it was significantly lower than SBRT group (P < 0.05). The mortality rate in the SBRT group was 16.7%, which was significantly higher than that in the interstitial brachytherapy group.ConclusionThe treatment method of interstitial brachytherapy is considered as an effective and safe tool by reducing the side effects of radiotherapy and increasing the radiation dose of radiotherapy.

Efficacy of redox nanoparticles for improving survival of transplanted cells in a mouse model of ischemic stroke.

The success of cell transplantation therapy for ischemic stroke is hindered by the low cell survival rate in poststroke brain, due in part to high free radical production and ensuing oxidative stress. We have developed redox nanoparticles to eliminate reactive oxygen species. In this study, we tested the protective efficacy of these redox nanoparticles in cell culture and a mouse model of ischemic stroke. Induced human dental pulp stem cells were subjected to oxygen-glucose deprivation and reoxygenation to recapitulate ischemia and reperfusion in the penumbra surrounding a cerebral infarct. Cell viability using WST-8 assay, apoptosis using TUNEL, free radicals using MitoSOX, and inflammatory cytokines using ELISA kit were measured in the presence and absence of redox nanoparticles after oxygen-glucose deprivation and reoxygenation. The scavenging activity of redox nanoparticles against reactive oxygen species was detected by electron spin resonance. Moreover, induced cells were transplanted intracerebrally into to the distal middle cerebral artery occlusion model with and without redox nanoparticles, and the survival rate measured. Cell viability was enhanced, while apoptosis, free radical generation, and inflammatory cytokine expression levels were reduced in cultures with redox nanoparticles. Further, reduced redox nanoparticles were detected in the cytoplasm, indicating free radical scavenging. Addition of redox nanoparticles also improved the survival rate of transplanted cells after 6 weeks in vivo. These redox nanoparticles may increase the applicability and success of induced stem cell therapy for ischemic stroke patents by promoting long-term survival.

Aging exaggerates pulpal pain sensation by increasing the expression levels of nociceptive neuropeptides and inflammatory cytokines

BackgroundDental pain is a main clinical problem in the elderly population and its assessment and treatment make special challenges for health care services. However, the age-induced alteration in dental pain perception and the underlying molecular mechanism(s) has not yet been fully clarified. MethodsHere, the effect of aging on nociceptive behaviors following inflammatory dental pulp pain was evaluated. Since prostaglandins, nociceptive neuropeptides, and inflammatory cytokines have critical roles in the development of aging as well as pain signaling, the expression levels of COX-2, CGRP, IL-1β, IL-6, TNF-α and its converting enzyme TACE were assessed in the trigeminal ganglion of young and aged rats with dental pain. Dental pulp pain was induced by intradental application of capsaicin (100 μg). The immunofluorescence (COX-2 and CGRP) and western blot techniques were used. ResultsThe data showed that aged animals have different pattern of pain. So that, the mean of nociceptive scores was significantly greater in aged rats at 10 and 15 min after capsaicin injection. In aged rats, dental pain was persisting over 7 h, while it was disappeared at 300 min in young rats. Molecular data showed that dental pain significantly increased the expression of COX-2, CGRP, IL-1β, IL-6, TNF-α and TACE in the trigeminal ganglion of the young and aged rats. In addition, the amount of those parameters, except TACE, in capsaicin-treated aged animals were significantly (p < 0.05) greater than those in capsaicin-treated young rats. ConclusionIt seems that the induction of pro-inflammatory cytokines in an acute inflammatory pulpal pain model may contribute, at least in part to the increased nociceptive behaviors and pain perception in aged rats.

Interferon lambda modulates proinflammatory cytokines production in PBMCs from patients with chronic kidney disease

BackgroundCKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFNλ plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFNλ with CKD is still poorly understood. ObjectiveTo analyze the correlation between IFNλ levels and pro-inflammatory cytokines, and to investigate the effect of IFNλ on PBMCs in patients with CKD. MethodsPBMCs were harvested from patients with CKD and healthy controls for measuring the expression level of inflammatory cytokines by RT-qPCR. Spearman correlation test was used to analyze correlation between IFNλ and cytokines as well as eGFR. PBMCs from healthy individuals and CKD patients were subjected to IFNλ protein stimulation. IL6, TNFα, IL10, ISG15 and MX1 mRNA level were measured by RT-PCR, STAT1 and phosphorylated STAT1 protein level were measured by Western blot. ResultsPatients with CKD showed higher levels of IFNλ in PBMCs compared to healthy controls. IFNλ mRNA levels were associated with cytokines and eGFR. The transcription of IL6, TNFα, and IL10 was significantly increased in healthy human PBMCs after IFNλ stimulation. In addition, IFNλ acts on PBMCs by p-STAT1 and ISG15 as well as MX1. ConclusionHigh expression of IFNλ was found in CKD patients and was associated with eGFR and disease-related cytokines. More importantly, IFNλ promoted the expression of pro-inflammatory cytokines in PBMCs, suggesting a potential pro-inflammatory role of IFNλ in CKD.

Nephroprotective effects of Acacia senegal against aflatoxicosis via targeting inflammatory and apoptotic signaling pathways

Aflatoxin B1 (AFB1) is a common environmental pollutant that poses a major hazard to both humans and animals. Acacia senegal (Gum) is well-known for having antioxidant and anti-inflammatory bioactive compounds. Our study aimed to scout the nephroprotective effects of Acacia gum (Gum) against AFB1-induced renal damage. Four groups of rats were designed: Control, Gum (7.5 mg/kg), AFB1 (200 µg/kg b.w) and AFB1-Gum, rats were co-treated with both Gum and AFB1. Gas chromatography-mass spectrometry (GC/MS) analysis was done to determine the phytochemical constituents in Gum. AFB1 triggered profound alterations in kidney function parameters (urea, creatinine, uric acid, and alkaline phosphatase) and renal histological architecture. Additionally, AFB1 exposure evoked up-regulation of mRNA expression levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), and nuclear factor kB p65 (NF-κB/P65) in renal tissue. The oxidative distress and apoptotic cascade are also instigated by AFB1 intoxication as depicted in down-regulated protein expression of the nuclear factor erythroid 2–related factor 2 (Nrf2) and superoxide dismutase type 1 (SOD1) along with upregulation of cytochrome c (Cyto c), and cleaved Caspase3 (Casp3–17 and 19) in renal tissue. In conclusion, current study obviously confirms the alleviating effects of Gum supplementation against AFB1-induced renal dysfunction, oxidative harm, inflammation, and cell death. These mitigating effects are suggested to be attributed to Gum's antioxidant and anti-inflammatory activities. Our results recommend Gum supplementation as add-on agents to food that might aid in protection from AFB1-induced nephrotoxicity.

Activation of aldehyde dehydrogenase-2 improves ischemic random skin flap survival in rats.

Random skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action. Modified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence. Alda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion. ALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.

Sodium thiosulfate ameliorates atopic dermatitis via inhibiting the activation of NLRP3 inflammasome

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1β expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.

Polydeoxyribonucleotide exerts opposing effects on ERK activity in human skin keratinocytes and fibroblasts.

Polydeoxyribonucleotide (PDRN) is a mixture of deoxyribonucleotides. It serves as an anti‑inflammatory and tissue‑regenerating agent. The mitogen‑activated protein kinase pathway modulates cell growth and collagen accumulation. It also regulates inflammation by suppressing the expression of proinflammatory cytokines. In the present study, it was attempted to elucidate the molecular mechanism of PDRN in skin healing by confirming the effects of PDRN treatment on skin keratinocytes and fibroblasts, and by assessing the levels of collagen and inflammatory cytokines regulated by the extracellular signal‑regulated kinase (ERK) pathway. The potential effects of PDRN on skin regeneration were investigated. Fibroblast and keratinocyte proliferation and migration were analyzed using the water‑soluble tetrazolium‑8 and wound healing assays. The upregulation of collagen synthesis by PDRN‑induced ERK activation was analyzed in fibroblasts with or without an ERK inhibitor. Inflammatory cytokine expression levels in keratinocytes were determined using reverse transcription‑quantitative polymerase chain reaction. PDRN promoted the proliferation and migration of keratinocytes and fibroblasts. However, PDRN‑induced ERK phosphorylation differed between keratinocytes and fibroblasts; PDRN increased ERK phosphorylation and collagen accumulation in fibroblasts, while it inhibited matrix metalloproteinase expression. By contrast, PDRN inhibited ERK phosphorylation in keratinocytes, and it decreased inflammatory cytokine expression levels. PDRN affects skin cell proliferation and migration, and collagen and inflammatory cytokine expression levels via ERK signaling. Overall, PDRN exerts a positive effect on skin regeneration, but the mechanism by which it promotes skin regeneration varies among different skin cell types.

Regulation of RIP1-Mediated necroptosis via necrostatin-1 in periodontitis.

To explore the mechanism of receptor-interacting protein 1 (RIP1)-mediated necroptosis during periodontitis progression. RIP3 and mixed lineage kinase domain-like protein (MLKL) have been detected to be upregulated in periodontitis models. Because RIP1 is involved in necroptosis, it might also play a role in the progression of periodontitis. An experimental periodontitis model in BALB/c mice was established by inducing oral bacterial infection. Western blotting and immunofluorescence analyses were used to detect RIP1 expression in the periodontal ligament. Porphyromonas gingivalis was used to stimulate L929 and MC3T3-E1. RIP1 was inhibited using small-interfering RNA. Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the effect of necroptosis inhibition on the expression of damage-associated molecular patterns and inflammatory cytokines. Necrostatin-1 (Nec-1) was intraperitoneally injected to inhibit RIP1 expression in mice. Necroptosis activation and inflammatory cytokine expression in periodontal tissue were verified. Tartrate-resistant acid phosphatase staining was applied to observe osteoclasts in the bone tissues of different groups. RIP1-mediated necroptosis was activated in mice with periodontitis. P. gingivalis induced RIP1-mediated necroptosis in L929 and MC3T3-E1 cells. After RIP1 inhibition, the expression levels of high mobility group protein B1 (HMGB1) and inflammatory cytokines were downregulated. After inhibiting RIP1 with Nec-1 in vivo, necroptosis was also inhibited, the expression levels of HMGB1 and inflammatory cytokines were downregulated, and osteoclast counts in the periodontal tissue decreased. RIP1-mediated necroptosis plays a role in the pathological process of periodontitis in mice. Nec-1 inhibited necroptosis, alleviated inflammation in periodontal tissue, and reduced bone resorption in periodontitis.

ELAVL1 promotes LPS-induced endothelial cells injury through modulation of cytokine storm

Sepsis is a life-threatening systemic organ dysfunction caused by the host's unregulated response to a widespread bacterial infection. Endothelial injury is a major pathophysiologic symptom of sepsis and is considered a critical factor in promoting the progression of disease severity. ELAV like RNA binding protein 1(ELAVL1) is a ubiquitously expressed RNA-binding protein that may play an important role during sepsis. Nonetheless, the molecular mechanisms of ELAVL1 on endothelial cell damage in sepsis have not been well defined. Here, we aimed to confirm the role of ELAVL1 in sepsis-induced endothelial cell damage using lipopolysaccharide (LPS)-induced zebrafish and endothelial cells (ECs) models. We found that zebrafish larvae treated with LPS exhibited systemic endothelial cell damage, mostly manifested as pericardial edema, curved tail, and impaired angiogenesis. LPS treatments also significantly induced the expression levels of inflammatory cytokines (interleukin-6 (IL-6), IL-8, and tumor necrosis factor (TNF)-α) in vivo. In vitro, we observed the increase of ELAVL1 cytoplasmic translocation with LPS treatment. Mechanistically, targeted disruption of the ELAVL1 gene decreased the expression of TNF-α, IL-6, and IL-8 during induction of sepsis and alleviated LPS-induced blood vessel injury in zebrafish. Taken together, our study indicates that ELAVL1 knockdown may alleviate sepsis-induced endothelial cells injury by suppressing cytokine storm. Our research suggests that inhibition of ELAVL1 could reduce the level of inflammatory cytokine production induced by LPS and protect against endothelial cell injury. ELAVL1 might be a potential therapeutic target to block endothelial cells injury associated with sepsis.

Antidiabetic and Immunoregulatory Activities of Extract of Phyllanthus emblica L. in NOD with Spontaneous and Cyclophosphamide-Accelerated Diabetic Mice.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)/Th2/Th17/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-γ and tumor necrosis α (TNF-α) by Th1 cells, and reduced interleukin (IL)-1β and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-β1 (TGF-β1) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4+ subsets T cell distribution of CD4+IL-17 and CD4+ interferon gamma (IFN-γ), but increased the CD4+ subsets T cell distribution of CD4+IL-4 and CD4+Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4+IL-17 and CD4+IFNγ, and increased CD4+IL-4 and CD4+Foxp3 compared with the Cyp-NOD Con group (p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-γ and TNF-α by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1β by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing β cells (brown), and but also enhanced the percentage of Bcl-2 (green)/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas β cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.

Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines.

To evaluate the effects and related mechanisms of electroacupuncture (EA) on irritable bowel syndrome (IBS). Male C57BL/6 mice were randomly allocated into normal, model, and EA groups. Experimental IBS mice models were established by exposure to water avoidance stress (WAS). Mice in the EA group were treated with EA at bilateral Tianshu (ST 25) and Zusanli (ST 36) for 7 consecutive days, 15 min each day. Abdominal withdrawal reflex (AWR) tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice. Expression levels of tight junction proteins (TJPs) and inflammatory cytokines in colon tissues were determined through immunofluorescence, real-time polymerase chain reactions (PCR) and Western blot assays. EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice. Moreover, EA promoted the expression of zonula occludens (ZO)-1, claudin-1, and occludin while suppressing the expression of interleukin (IL)-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-αin water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) mice. EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.

The Anti-inflammatory Effect of Ginger Extract on the Animal Model of Multiple Sclerosis.

Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes. To investigate ginger extract's effect on reducing inflammation and improving the symptoms in the EAE model. The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation. The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups. The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.

Bifidobacterium bifidum E3 Combined with Bifidobacterium longum subsp. infantis E4 Improves LPS-Induced Intestinal Injury by Inhibiting the TLR4/NF-κB and MAPK Signaling Pathways In Vivo.

Changes in the functions of the intestinal barrier occur in parallel with the development of sepsis. The protection by Bifidobacterium strains (BB, BL, BB12, and BLBB) was evaluated in mice injected with lipopolysaccharide (LPS). The results revealed an increase in the ratio of ileal villus length to crypt depth in the BLBB group compared with that in the LPS group, as were the number of IgA+ plasma, CD4+/CD8+ T, and dendritic cells. The levels of diamine oxidase (DAO) and d-lactic acid in the serum were lessened in the BLBB group after LPS injection compared with that in the LPS group. In addition, the BLBB group exhibited an increased expression level of tight junction proteins (zonula occludens-1, occludin, and claudin-1), mucin (MUC2) mRNA, reduced NFκB/MAPK signaling pathways, and decreased expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α). The BLBB group enriched the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, Clostridia_Ucg-014, and Alistipes, resulting in an increase in strains producing short-chain fatty acids. Furthermore, the BLBB group leads to higher levels of deoxycholic acid and biosynthesized linoleate. This study suggested that the BLBB group could enhance the capacity of the intestinal barrier and intestinal mucosal immunity, reduce intestinal inflammation, and improve the composition of gut microbiota. Bifidobacterium bifidum E3 combined with Bifidobacterium longum subsp. infantis E4 may thus serve as a probiotic against the intestinal injury caused by LPS.

DNA damage-inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models.

Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage-inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis. DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro-CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT-PCR. Bone marrow-derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast-specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti-inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis.

Circular RNA DHTKD1 targets miR‑338‑3p/ETS1 axis to regulate the inflammatory response in human bronchial epithelial cells.

Asthma is a chronic inflammatory airway disease and the airway epithelium is involved in airway inflammation and innate immunity. However, whether circular RNA (circRNA) is involved in the pathogenesis of asthma remains unclear. The present study aimed to determine the functions and molecular mechanisms of circRNA targeting dehydrogenase E1 (circDHTKD1) in the inflammation response of human bronchial epithelial cells. BEAS-2B cells were stimulated with lipopolysaccharide (LPS) to establish a model of in vitro airway inflammation. Cell viability was assessed using Cell Counting Kit-8 assay. CircDHTKD1 was characterised by nucleocytoplasmic isolation and Sanger sequencing. The RNA expression levels of circDHTKD1, microRNA (miR)-338-3p and potential ERK pathway downstream genes were evaluated by reverse transcription-quantitative polymerase chain reaction. Western blot analysis was performed to measure associated protein levels. The levels of inflammatory cytokines were detected by ELISA. The interaction between circDHTKD1 and miR-338-3p was confirmed by dual-luciferase reporter assay. circDHTKD1 expression was significantly upregulated by LPS treatment, whereas miR-338-3p expression was decreased. Furthermore, circDHTKD1 directly targeted miR-338-3p, which negatively regulated expression of E26 transformation specific-1 (ETS1). Inflammatory cytokine and ETS1 expression levels decreased following transfection with small interfering RNA targeting circDHTKD1 or miR-338-3p mimics. In addition, co-transfection with miR-338-3p inhibitor reversed the effects caused by circDHTKD1 knockdown. The knockdown of ETS1 in LPS-induced BEAS-2B cells resulted in decreased cytokine production and inhibition of the ERK signalling pathway. Overall, these results suggested that the knockdown of circDHTKD1 alleviated the LPS-induced production of inflammatory cytokines and activation of the ERK pathway in BEAS-2B cells through the miR-338-3p/ETS1 axis. In summary, circDHTKD1 exacerbated LPS-triggered inflammation responses in BEAS-2B cells by regulating ETS1 expression by interacting with miR-338-3p, suggesting that circDHTKD1 may serve as a potential therapeutic target against asthma.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

Perilla, sunflower, and tea seed oils as potential dietary supplements with anti-obesity effects by modulating the gut microbiota composition in mice fed a high-fat diet.

Obesity has become a serious public health problem with its alarmingly increasing prevalence worldwide, prompting researchers to create and develop several anti-obesity drugs. Here, we aimed to investigate the protective effects of perilla seed oil (PSO), sunflower oil (SFO), and tea seed oil (TSO) against obesity through the modulation of the gut microbiota composition and related metabolic changes in mice fed a high-fat diet (HFD). Mice were divided into six equal groups: ND (normal diet); HFD; ORL (HFD supplemented with 20mg/kg body weight of orlistat); PSO, SFO, and TSO (HFD supplemented with 2g/kg body weight of PSO, SFO, and TSO, respectively). Our findings showed that PSO, SFO, and TSO supplementation significantly reduced body weight, organ weight, blood glucose, lipopolysaccharides (LPS), insulin resistance, and improved serum lipid levels (TG, TC, LDL-C, and HDL-C). Meanwhile, the three treatments alleviated oxidative stress and hepatic steatosis and reduced liver lipid accumulation. Relative mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) and lipid synthesis-related genes (PPAR-γ, FAS, and SREBP-1) were down-regulated, while β-oxidation-related genes (PPAR-α, CPT1a, and CPT1b) were up-regulated in the liver tissue of treated mice. Besides, dietary oil supplementation alleviated HFD-induced gut microbiota dysbiosis by promoting gut microbiota richness and diversity, decreasing the Firmicutes-to-Bacteroidetes ratio, and boosting the abundance of some healthy bacteria, like Akkermansia. PSO, SFO, and TSO supplementation could alleviate inflammation, oxidative stress, and hepatic steatosis, likely by modulating the gut microbiota composition in HFD-fed mice.

Ischemic postconditioning protects against acute kidney injury after limb ischemia reperfusion by regulating HMGB1 release and autophagy

Ischemic postconditioning (I-PostC) has a protective effect against acute kidney injury (AKI) induced by limb ischemia–reperfusion (LIR); however, the exact mechanism remains to be elucidated. Our study aims to investigate the potential involvement of high-mobility group box 1 protein (HMGB1) and autophagy in renoprotection generated by I-PostC. A rat model of LIR-induced AKI was established and rats were randomly assigned to five groups: (i) sham-operated control, (ii) I/R, (iii) I/R + I-PostC, (iv) I/R + I-PostC + rapamycin (autophagy activator), and (v) I/R + I-PostC + 3-methyladenine (autophagy inhibitor). Morphological changes in the kidneys were assessed by histology, and ultrastructural changes in renal tubular epithelial cells and glomerular podocytes were observed by transmission electron microscopy. The levels of kidney function parameters, serum inflammatory factors, and autophagy markers were detected. The results showed that the levels of HMGB1, Beclin1, LC3-II/LC3-I, and inflammatory cytokines (TNF-α and IL-6) were significantly higher in the I/R group compared to the sham control in serum and in renal tissues. I-PostC significantly reduced the levels of HMGB1, Beclin1, LC3-II/LC3-I, and inflammatory cytokines in renal tissues and improved renal function. Renal histopathology and ultrastructural observations indicated that I-PostC alleviated renal tissue injury. In addition, rapamycin (autophagy activator) treatment increased the levels of inflammatory cytokine expression levels and decreased renal function, reversed the protective effect of I-PostC against LIR-induced AKI. In conclusion, I-PostC could play a protective role against AKI by regulating the release of HMGB1 and inhibiting autophagy activation.

Abdominal Aortic Endograft Implantation Immediately Induces Vascular Stiffness Gradients That May Promote Adverse Aortic Neck Dilatation: Results of A Porcine Ex Vivo Study.

Endovascular aortic repair (EVAR) is the method of choice for most abdominal aortic aneurysm (AAA) patients requiring intervention. However, chronic aortic neck dilatation (AND) following EVAR progressively weakens the structural seal between vessel and endograft and compromises long-term results of the therapy. This experimental ex vivo study seeks to investigate mechanisms of AND. Porcine abdominal aortas (n=20) were harvested from slaughterhouse pigs and connected to a mock circulation. A commercially available endograft was implanted (n=10) or aortas were left untreated as controls (n=10). Vascular circumferential strain was assessed via ultrasound in defined aortic segments as a parameter of aortic stiffness. Histology and aortic gene expression analysis were performed to investigate potential changes of aortic wall structure and molecular differences due to endograft implantation. We found that endograft implantation acutely induces a significant stiffness gradient directly at the interface between stented and unstented aortic segments under pulsatile pressure. Comparing stented aortas with unstented controls, we detected increased aortic expression levels of inflammatory cytokines (Il6 and Ccl2) and matrix metalloproteinases (Mmp2 and Mmp9) after 6 hours of pulsatile pressurization. This effect, however, was abolished when repeating the same experiment under 6 hours of static pressure. We identified endograft-induced aortic stiffness gradients as an early trigger of inflammatory aortic remodeling processes that might promote AND. These results highlight the importance of adequate endograft designs to minimize vascular stiffness gradients and forestall late complications, such as AND. AND may compromise the long-term results following endovascular aortic repair. However, the mechanisms behind the underlying detrimental aortic remodeling are still unclear. In this study we find that endograft-induced aortic stiffness gradients induce an inflammatory aortic remodeling response consistent with AND. This novel pathomechanistic insight may guide the design of new aortic endografts that minimize vascular stiffness gradients and forestall late complications such as AND.