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Background: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation., Purpose: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation., Methods: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay., Results: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation., Conclusion: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Autologous fat grafting is a common method for soft tissue defect repair. However, the high absorption rate of transplanted fat is currently a bottleneck in the process. Excessive inflammation is one of the main reasons for poor fat transplantation. Salvianolic acid B (Sal-B) is a herbal medicine that shows promise for improving the effectiveness of fat transplantation., Objective: The aim of this study was to improve fat graft survival by injecting Sal-B into fat grafts locally., Methods: In vivo, 0.2 mL of Coleman fat was transplanted into nude mice along with Sal-B. The grafts were evaluated by histologic analysis at 2, 4, and 12 weeks posttransplantation and by microcomputed tomography at 4 weeks posttransplantation. In vitro ribonucleic acid sequencing, cell proliferation assays, anti-inflammatory activity assays, molecular docking studies, and kinase activity assays were performed in RAW264.7 cells to detect the potential mechanism., Results: Sal-B significantly improved fat graft survival and attenuated adipose tissue fibrosis and inflammation. Sal-B also inhibited the polarization of M1 macrophages in fat grafts. In vitro, Sal-B inhibited the proliferation and activation of inflammatory pathways in RAW264.7 cells. In addition, Sal-B had an inhibitory effect on NF-κB (nuclear factor κ light polypeptide gene enhancer in B cells) signaling. This bioactivity of Sal-B may result from its selective binding to the kinase domain of the inhibitor of NF-κB kinase subunit β., Conclusions: Sal-B could serve as a promising agent for improving the effect of fat transplantation by inhibiting the polarization of M1 macrophages through NF-κB signaling., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population., Methods: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model., Results: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36)., Conclusions: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study., (© 2022. The Author(s).)

Context: Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear., Objective: To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism., Materials and Methods: A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups ( n  = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining., Results: The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO 2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression., Discussion and Conclusions: Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.

Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle dilation and cardiac dysfunction, eventually developing into heart failure. Mzb1 (Marginal zone B and B1 cell specific protein 1) is a B-cell-specific and endoplasmic reticulum-localized protein. Mzb1 is an inflammation-associated factor that participates a series of inflammatory processes, including chronic periodontitis and several cancers. In this study we investigated the role of Mzb1 in experimental models of MI. MI was induced in mice by ligation of the left descending anterior coronary artery, and in neonatal mouse ventricular cardiomyocytes (NMVCs) by H 2 O 2 treatment in vitro. We showed that Mzb1 expression was markedly reduced in the border zone of the infarct myocardium of MI mice and in H 2 O 2 -treated NMVCs. In H 2 O 2 -treated cardiomyocytes, knockdown of Mzb1 decreased mitochondrial membrane potential, impaired mitochondrial function and promoted apoptosis. On contrary, overexpression of Mzb1 improved mitochondrial membrane potential, ATP levels and mitochondrial oxygen consumption rate (OCR), and inhibited apoptosis. Direct injection of lentiviral vector carrying Len-Mzb1 into the myocardial tissue significantly improved cardiac function and alleviated apoptosis in MI mice. We showed that Mzb1 overexpression significantly decreased the levels of Bax/Bcl-2 and cytochrome c and improved mitochondrial function in MI mice via activating the AMPK-PGC1α pathway. In addition, we demonstrated that Mzb1 recruited the macrophages and alleviated inflammation in MI mice. We conclude that Mzb1 is a crucial regulator of cardiomyocytes after MI by improving mitochondrial function and reducing inflammatory signaling pathways, implying a promising therapeutic target in ischemic cardiomyopathy.

Acute pancreatitis (AP), a common abdominal inflammatory disorder, is characterized by premature intracellular activation of digestive proteases within pancreatic acini and a consecutive systemic inflammatory response. Although the mechanism remains to be fully understood, inflammation is the main cause of pancreatic damage in AP. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits anti-inflammatory and anti-apoptotic properties in vitro . However, its potential beneficial effect in AP has not been demonstrated. This study aimed to investigate the effects and underlying mechanisms of DSC in experimental AP in mice. We found that DSC suppressed inflammatory responses in AP by inhibiting the activation of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) and nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome. Furthermore, treatment with DSC modulated the infiltration of neutrophils and the phenotypes of macrophages in mice induced with AP. Interestingly, we found that the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and its regulated antioxidant enzyme heme oxygenase-1 (HO-1), which modulate inflammatory activities, was significantly increased in DSC-treated groups. Together, our findings demonstrate that DSC alleviates pancreatic inflammation and damage in AP by inhibiting the activation of NF-κB, STAT3, and NLRP3 inflammasome and modulating immune cell responses.

Background: The American Joint Committee on Cancer has recently revised the tumor-node-metastasis (TNM) staging system on thyroid cancer, which illustrated that the cut-off age for predicting mortality has elevated from 45 to 55 years old. We aimed to investigate the inflammation index based on hematological parameters to predict the clinical characteristics of elderly papillary thyroid cancer (PTC) patients with an inferior prognosis., Methods: We retrospectively analyzed 558 patients newly diagnosed with PTC from January 2013 to December 2017, and 82 out of the 558 patients were over 55 years old. Receiver operating characteristic (ROC) study and univariate and multivariate logistic analysis was conducted to evaluate the diagnostic value of these preoperative inflammation indexes in PTC patients ≥ 55 years of age., Results: Elevated neutrophils were prognostic of bilaterality (area under the ROC curve (AUC) = 0.673, p = 0.023) and lymph node metastasis (AUC = 0.649, p = 0·020). Decreased mean platelet volume (MPV) and platelet distribution width (PDW) were prognostic of coexistence with Hashimoto's thyroiditis (AUC = 0.736, p = 0.016; AUC = 0.721, p = 0.024). Elevated lymphocyte and lymphocyte-to-monocyte ratio (LMR) were prognostic of advanced TNM stage (AUC = 0.691, p = 0.029; AUC = 0.680, p = 0.040). Meanwhile, the logistic regression model further revealed that LMR ≥ 5.45 was an independent risk factor for the advanced TNM stage (odds ratio (OR) = 7.306, p = 0.036)., Conclusions: The preoperative neutrophils, lymphocytes, MPV, PDW, LMR were all prognostic. More importantly, the increased in LMR independently contributed to the advanced TNM stage of PTC patients ≥ 55 years.

Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation of Wnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases., Competing Interests: The authors declare no conflict of interest.

Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

Background: Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments., Methods: Plasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1-2 (n = 37), CKD 3-4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure., Results: Plasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1-2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2'-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3-4 with 8-OHdG and sVCAM-1; and in CKD 1-2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01-1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01-1.06, p = 0.03) after adjusting for all confounders., Conclusions: Plasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients., Competing Interests: This study was supported by grants from Baxter Healthcare Corporation and Amgen Inc to Karolinska Institutet. The grant from Baxter Healthcare Corporation was a general grant to Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, to support research activities at Karolinska Institutet to promote the understanding and treatment of renal disease which made it possible to carry out this and other studies. The grant from Amgen Inc was given to Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, to support two observational studies on inflammation in dialysis patients treated by hemodialysis and peritoneal dialysis respectively. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κ B activation and modulated NF- κ B-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF- κ B inflammatory pathways in acinar cells, thereby protecting against AP.

Objective: To investigate the relationship between low-grade inflammation (LI) and increased arterial stiffness in Chinese youth and adolescents with newly-diagnosed type 2 diabetes mellitus (T2DM)., Methods: Ninety-eight subjects aged 10 to 24 years with newly-diagnosed T2DM were investigated for findings of general inflammation. Anthropometric measurements were taken. Data related to arterial stiffness [brachial artery distensibility (Branch D), augmentation index (AIx), carotid-femoral pulse wave velocity (CF-PWV)] were collected. The subjects were divided into a non-LI group (NLI, n=42) and a LI group (n=56) according to their high-sensitivity C-reactive protein (Hs-CRP) levels., Results: There were no significant differences in age and gender between the LI group and the NLI group. CF-PWV and AIx values of the LI group were higher than those of the NLI group (p<0.01), while Branch D values were lower in the LI group (p<0.01). Branch D, CF-PWV, and AIx values correlated significantly with Hs-CRP overall (r=-0.32, 0.34, 0.33, all p<0.01). Multivariate models revealed that in either group (LI or NLI), Hs-CRP, as a continuous variable, was an independent determinant of arterial stiffness parameters even after adjusting for other risk factors., Conclusion: Newly-diagnosed T2DM youth and adolescents with LI present a more adverse cardiovascular disease risk profile and stiffer arteries. Hs-CRP levels correlated with arterial stiffness parameters and constituted an independent determinant of arterial stiffness.

Cerebrovascular accumulation of amyloid-β (Aβ) peptides in Alzheimer's disease (AD) may contribute to disease progression through Aβ-induced microvascular endothelial pathogenesis. Pinocembrin has been shown to have therapeutic effects in AD models. These effects correlate with preservation of microvascular function, but the effect on endothelial cells under Aβ-damaged conditions is unclear. The present study focuses on the in vitro protective effect of pinocembrin on fibrillar Aβ(1-40) (fAβ(1-40)) injured human brain microvascular endothelial cells (hBMECs) and explores potential mechanisms. The results demonstrate that fAβ(1-40)-induced cytotoxicity in hBMECs can be rescued by pinocembrin treatment. Pinocembrin increases cell viability, reduces the release of LDH, and relieves nuclear condensation. The mechanisms of this reversal from Aβ may be associated with the inhibition of inflammatory response, involving inhibition of MAPK activation, downregulation of phosphor-IKK level, relief of IκBα degradation, blockage of NF-κB p65 nuclear translocation, and reduction of the release of proinflammatory cytokines. Pinocembrin does not show obvious effects on regulating the redox imbalance after exposure to fAβ(1-40). Together, the suppression of MAPK and the NF-κB signaling pathways play a significant role in the anti-inflammation of pinocembrin in hBMECs subjected to fAβ(1-40). This may serve as a therapeutic agent for BMEC protection in Alzheimer's-related deficits.

Substance P, a neuropeptide belonging to the tachykinin family is a pleiotropic peptide with specific neural activities and involved in immunomodulation and antimicrobial host defense. It has been found to modulate a variety of inflammatory processes, including acute pancreatitis, sepsis, systemic inflammatory response syndrome and asthma. Also notably, substance P shares common bio-physical and -chemical properties such as low molecular mass, cathionicity and amphipathicity with antimicrobial peptides. It is therefore suggested to take part in host defense at specialized locations. The review aims to highlight undated understanding on substance P in inflammation, allergy and its antimicrobial activities with potential implications in infection and host defense. Therapeutic implications of the peptide, modulators of peptide expression and receptor signalling will be highlighted in each topic. Taken together, these topics will be of significant values for future pharmaceutical investigation and application of the field.

Introduction: C1q/TNF-related Protein-3 (CTRP3) is a novel adipokine with multiple effects such as lowering glucose levels, inhibiting glyconeogenesis in the liver, and increasing angiogenesis and anti-inflammation. But little is known about the effects of CTRP3 on insulin resistance in adipose tissue. This study aims to investigate the effects and mechanisms of CTRP3 on the insulin sensitivity of 3T3-L1 adipocytes., Material and Methods: Insulin resistant 3T3-L1 adipocytes were induced by palmic acid cultivation. Such adipocytes were treated with recombinant CTRP3 protein at different concentrations (0, 10, 50, 1,250 ng/mL) for 12 hours, and at a concentration of 250 ng/mL for differing times (2, 6, 12, and 24 h). Another group was pre-treated with wortmannin, the special inhibitor of phosphatidylinositol-4,5- bisphosphate 3-kinase (PI3K), for 20 minutes before the treatment with 250 ng/mL CTRP3. The glucose consumption, the glucose uptake, the expression and release of tumour necrosis factor α (TNF-α) and interleukin-6(IL-6) in supernatant, and the protein relative expression of PI3K and protein kinase B (PKB)(ser437) were detected., Results: Compared to the control group, glucose consumption in the CTRP3 intervention group at concentrations of 10, 50, 250, and 1,250 ng/mL was increased by 22.1%, 42.9%, 76.6% and 80.5% respectively (all P < 0.01); the glucose uptake was increased by 39.0%, 68.0%, 108.0% and 111.0% respectively (all P < 0.01); the content of TNF-α in the culture media of CTRP3 (10, 50, 250 ng/mL) intervention group was decreased by 7.6% (P > 0.05), 13.0% (P < 0.05) and 17.4% (P < 0.01) respectively; the content of IL-6 was decreased by 7.1%, 12.4% and 17.1% respectively (all P < 0.01); the protein relative expression of PI3K was increased by 0.63-, 1.00- and 1.36-fold respectively (all P < 0.01), and PKB(ser437) increased by 0.65-, 1.61- and 1.93-fold respectively (all P < 0.01); the mRNA relative expression of GLUT-4 was increased by 23.0%, 47.0% and 62.0% respectively (all P < 0.01). After the treatment with wortmannin, glucose consumption, glucose uptake, PI3K and PKB(ser437) protein relative expression, as well as GLUT-4 mRNA relative expression, was decreased by 53.2%, 44.7%, 43.4%, 56.1 and 30.9% respectively (all P < 0.01)., Conclusions: CTRP3 could improve insulin sensitivity of insulin resistant 3T3-L1 adipocytes by decreasing inflammation and ameliorating insulin signalling transduction, indicating that CTRP3 may be a new target for the prevention and cure of insulin resistance and type 2 diabetes.

Acute pancreatitis is an inflammatory disorder of the pancreas. Protein kinase C (PKC) δ plays an important role in mediating chemokine production in mouse pancreatic acinar cells. This study aims to investigate the role of PKC δ in the pathogenesis of acute pancreatitis and to explore the mechanisms through which PKC δ mediates pro-inflammatory signaling. Acute pancreatitis was induced in mice by ten hourly intraperitoneal injections of caerulein. PKC δ translocation inhibitor peptide (δV1-1) at a dose of 1.0 mg/kg or Tat (carrier peptide) at a dose of 1.0 mg/kg was administered to mice either 1 h before or 1 h after the first caerulein injection. One hour after the last caerulein injection, the mice were killed and pancreas, lungs, and blood were collected. Prophylactic and therapeutic treatment with δV1-1 attenuated caerulein-induced plasma amylase levels and pancreatic edema. Treatment with δV1-1 decreased myeloperoxidase activity and monocyte chemotactic protein-1 levels in both pancreas and plasma. PKC δ mediated acute pancreatitis by activating pancreatic nuclear factor κB, activator protein-1, and mitogen-activated protein kinases. Moreover, blockade of PKC δ attenuated lung myeloperoxidase activity and edema. Histological examination of pancreatic and lung sections confirmed protection against acute pancreatitis. Treatment with Tat had no protective effect on acute pancreatitis. Blockade of PKC δ represents a promising prophylactic and/or therapeutic tool for the treatment of acute pancreatitis.

Background: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. Methods: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. Results: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322–1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196–17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). Conclusions: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke. [ABSTRACT FROM AUTHOR]

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases. [ABSTRACT FROM AUTHOR]

• The adipokine chemerin is involved in atherosclerosis-related pathological processes. • The adipokine chemerin as a specific biomarker for atherosclerosis will be explored in prospective studies. • The precise mechanism regulating adipokine chemerin during the atherosclerosis process deserve to be further explored. Atherosclerosis (AS), a chronic arterial disease, is characterized by endothelial dysfunction, inflammatory reactions and lipid accumulation in parallel with aberrant angiogenesis and vascular smooth muscle cell (VSMC) proliferation. Adipose tissue has been suggested to have an integral influence on metabolism and endocrine secretion, while there have been increasing concerns about the possible involvement of adipokines in cardiovascular diseases, including AS. Here, we focused on chemerin, an adipokine highly expressed in adipose tissue, with strong evidence of an association with inflammation, endothelial dysfunction, metabolic disorder, aberrant angiogenesis, VSMC proliferation and calcification. In this review, we discuss chemerin and its receptors in the pathogenesis of AS. However, the existing data assign various, even contradictory, roles to chemerin in atherosclerosis, such as inhibiting vascular calcification and impairing endothelial function. Current studies focusing on its anti- and pro-atherogenic effects have pinpointed its distinct role in specific cell types and contexts in the pathogenesis of atherosclerosis. Therefore, the gaps in current knowledge regarding the specific role played by chemerin in the etiology of AS require additional future studies. It seems reasonable to suggest that targeted chemerin therapy can be developed as an innovative approach for treating AS. [ABSTRACT FROM AUTHOR]

We have previously reported a novel compound [4‐(2‐acetoxy‐3‐((R)‐3‐(benzylthio)‐1‐methoxy‐1‐oxopropan‐2‐ylamino)‐3‐oxopropyl)‐1,2‐phenylene diacetate (DSC)], derived from danshensu, exhibits cytoprotective activities in vitro. Here, we investigated the effects and underlying mechanisms of DSC on dextran sodium sulphate (DSS)‐induced experimental colitis. We found that DSC treatment afforded significant protection against the development of colitis, evidencing by suppressed inflammatory responses and enhanced barrier integrity. Intriguingly, DSC specifically down‐regulated DSS‐induced colonic NADPH oxidase 4 (Nox4) expression, accompanied by a balanced redox status, suppressed nuclear factor‐κB (NF‐κB) and NLRP3 inflammasome activation and up‐regulated nuclear factor (erythroid‐derived 2)‐like 2 and haeme oxygenase‐1 expression. In vitro study also demonstrated DSC also markedly decreased Nox4 expression and activity associated with inhibiting reactive oxygen species generation, NF‐κB activation and NLRP3 inflammasome activation in bone marrow‐derived macrophages. Either lentiviral Nox4 shRNA‐mediated Nox4 knockdown or Nox4‐specific small‐interfering RNA mimicked effects of DSC by suppressing NLPR3 inflammasome activation to alleviate experimental colitis or inflammatory macrophage response. Collectively, our results provide the first evidence that DSC ameliorates experimental colitis partly through modulating Nox4‐mediated NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease characterized by memory loss and cognitive impairment. The major characteristics of AD are amyloid β plaques, apoptosis, autophagy dysfunction, neuroinflammation, oxidative stress, and mitochondrial dysfunction. These are mostly used as the significant indicators for selecting the effects of potential drugs. It is imperative to explain AD pathogenesis and realize productive treatments. Although the currently used chemical drugs for clinical applications of AD are effective in managing the symptoms, they are inadequate to achieve anticipated preventive or therapeutic outcomes. There are new strategies for treating AD. Traditional Chinese Medicine (TCM) has accumulated thousands of years of experience in treating dementia. Nowadays, numerous modern pharmacological studies have verified the efficacy of many bioactive ingredients isolated from TCM for AD treatment. In this review, representative TCM for the treatment of AD are discussed, and among these herbal medicines, the Lamiaceae family accounts for the highest proportion. It is concluded that monomers and extracts from TCM have potential therapeutic effect for AD treatment. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications. [ABSTRACT FROM AUTHOR]

Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear. This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets. The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein. BDE inhibited the expression of TNF-α, IL-1β, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1β , and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway. BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5. Methods: Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 –normal S-Alb and normal hsCRP (reference); Group 2 –low S-Alb and normal hsCRP; Group 3—normal S-Alb and high hsCRP; Group 4—low S-Alb and high hsCRP. Survival over 60 months was analyzed. Results: In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06–2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique. Conclusions: Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients. [ABSTRACT FROM AUTHOR]

Obesity is associated with a cluster of metabolic disorders and systemic low-grade inflammation involving multiple organs. Recent findings have suggested that intestine is a key organ altered in response to high fat diet (HFD) feeding. Probiotics mainly lactobacillus strains have earlier been implicated in alleviating metabolic disorders. Here we aimed to examine the effects of a naturally occurring butyrate-producing probiotic clostridium butyricum CGMCC0313.1 (CB0313.1) in limiting the development of HFD-induced obesity. Mice treated with CB0313.1 exhibited reduced lipid accumulation in liver and serum, lower circulating insulin levels and improved glucose tolerance and insulin sensitivity. Furthermore, CB0313.1 administration reversed the HFD-induced colonic inflammation as evidenced by reduced tumor necrosis factor (TNF)-α level and increases the interleukin (IL)-10 and IL-22 levels in colon tissue. Additionally to colonic inflammation, CB0313.1 also reduced the colon permeability by upregulating the tight junction (TJ) proteins (claudin-1 and occludin) and contributed to a decreased circulating endotoxin level. In colon content, CB0313.1 administration restored the reduced production of butyrate and other short chain fatty acids (SCFAs) caused by HFD feeding. In adipose tissue, lower transcriptional levels of pro-inflammatory TNF-α, IL-6, IL-1β and monocyte chemotactic protein (MCP)-1 in adipose tissue were observed in CB0313.1-treated mice. Collectively, our data demonstrated that CB0313.1, targeting colon inflammation and permeability, ameliorated HFD-induced obesity, insulin resistance as well as adipose inflammation. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between triglyceride to high-density lipoprotein cholesterol ( TG/ HDL-C) ratio and carotid intima-medial thickness ( CIMT) in Chinese youth and adolescents with newly diagnosed type 2 diabetes mellitus ( T2DM). Methods Ninety-eight subjects aged 10-24 yr with newly-diagnosed T2DM had general inflammation, anthropometric, laboratory and CIMT data collected, and were divided into three groups based on TG/ HDL-C tertiles. Results There were no significant differences in gender, age, fasting plasma glucose ( FPG), hemoglobin A1c ( HbA1c), and carotid arterial diameter ( CAD) among the groups based on TG/ HDL-C tertiles. Across TG/ HDL-C tertiles, there was a significant progressive increase in body mass index ( BMI), systolic blood pressure ( SBP), diastolic blood pressure ( DBP), homeostasis model assessment-estimated insulin resistance ( HOMA-IR), TG, total cholesterol ( TC), low-density lipoprotein-cholesterol ( LDL-C) and CIMT (all P < 0.01 or P < 0.05), while HDL-C was decreased significantly across the groups ( P < 0.01). In general linear regression model, TG/ HDL-C was an independent determinant of CIMT even after adjusting for BMI, SBP, DBP, TG, TC, LDL-C, HDL-C, HbA1c and HOMA-IR. Conclusion TG/ HDL-C ratio, the marker of small dense LDL particles, is an independent determinant of CIMT in Chinese youth and adolescents with newly diagnosed T2DM, and may be a simple and helpful tool in predicting the increased CIMT in such patients. [ABSTRACT FROM AUTHOR]

Background: Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. Methods and Results: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. Conclusions: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI. [ABSTRACT FROM AUTHOR]

• Angiopoietin-like proteins are involved in atherosclerosis-related pathological processes. • Angiopoietin-like proteins can be the roles as independent predictive value of biomarkers for atherosclerosis therapy. • The precise mechanism that Angiopoietin-like proteins regulate atherosclerosis process deserve to be further explored. Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral artery disease. Additional evidence is emerging that the angiopoietin-like (ANGPTL) family of proteins participate in the pathology of this disease process via endothelial dysfunction, inflammation, dyslipidemia, calcification, foam cell formation and platelet activation. This review summarizes current knowledge on the ANGPTL family of proteins in atherosclerosis related pathological processes. Moreover, the potential value of ANGPTL family proteins as predictive biomarkers in atherosclerosis is discussed. Given the attractive role of ANGPTL3, ANGPTL4, ANGPTL8 in atherosclerotic dyslipidemia via regulation of lipoprotein lipase (LPL), antisense oligonucleotide or/and monoclonal antibody-based inactivation of these proteins represent potential atherosclerotic therapies. [ABSTRACT FROM AUTHOR]

Sparstolonin B (SsnB), an isocoumarin compound isolated from the tubers of both Sparganium stoloniferum and Scirpus yagara , has been reported to have anti-inflammatory effects. However, whether SsnB has anti-inflammatory effects on LPS-stimulated 3T3-L1 adipocytes remains unclear. In this study, we investigated the effects of SsnB on adipocyte inflammation in 3T3-L1 adipocytes and anti-obesity properties in high fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes were pretreated with SsnB 1 h before LPS treatment. The expression of MCP-1, IL-6, TNF-α, and IL-10 were measured by qRT-PCR and ELISA. The expression of PPAR-γ, TLR4 and NF-κB were detected by western blotting. SsnB was administered to HFD-induced obese rats to confirm its effects in vivo. Our results showed that SsnB dose-dependently inhibited LPS-induced MCP-1, IL-6, and TNF-α production. SsnB was found to inhibit LPS-induced TLR4 expression and NF-κB activition. Furthermore, SsnB was found to activate PPAR-γ and the inhibitory effects of SsnB on MCP-1, IL-6, and TNF-α production can be reversed by PPAR-γ antagonist GW9662. In vivo, SsnB was found to reduce the body weight of rats fed with HFD. SsnB also inhibited the levels of serum triglyceride (TG) and cholesterol (TC) induced by HFD. In conclusion, the results suggested that SsnB could reduce HFD-induced obesity in rats and inhibited LPS-induced cytokines production in 3T3-L1 adipocytes by activating PPAR-γ. [ABSTRACT FROM AUTHOR]

Gerberae Piloselloidis Herba (GPH), a commonly used traditional medicine in China, is derived from Gerbera piloselloides (Linn.) Cass. It is featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial, anti-tumor, uterine analgesia, and immunity-enhancing. With a long history of medication in ethnic minority areas in China, it is often used as an effective treatment for cough and sore throat as well as allergic asthma. Although our previous investigation also has discovered GPH performed effective treatment on allergic asthma, its underlying mechanism remains unclear. This research aims to reveal the pharmacological mechanism of GPH in the treatment for allergic asthma through combination of plasma pharmacology and network pharmacology. Firstly, the components of GPH in blood samples were identified using UHPLC- Q-Orbitrap HRMS. An interaction network of "compound-target-disease" was constructed based on the compounds confirmed in blood and on their corresponding targets of allergic asthma acquired from disease gene databases, predicting the possible biological targets and potential signal pathways of GPH with the network pharmacology analysis. Then, a molecular docking between the blood ingredients and the core targets was carried out using the Autodock Vina software. Subsequently, after establishing a mouse model with allergic asthma induced by ovalbumin (OVA), the effect of GPH on allergic asthma was evaluated by analyzing a series of indicators including behavior, lung pathological changes, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF). Finally, the key pathway and targets predicted by network pharmacology and molecular docking were further verified using Western blot analysis. Eleven chemical constituents (such as arbutin, neochlorogenic acid, chlorogenic acid, etc.) were identified through the analysis of plasma samples, on which basis a total of 142 genes intersecting GPH and allergic asthma were collected by network pharmacology. After performing enrichment analysis of these genes in gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), it was found that arbutin-related targets mainly focused on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signal pathway, while luteolin and marmesin -related targets tended to locate at Interleukin-17 (IL-17) signal pathway. Meanwhile, the findings of molecular docking suggested that such components as arbutin, luteolin and marmesin entering into blood had good binding with the core targets related to PI3K/Akt and IL-17 pathways. In addition, GPH improved the OVA-induced asthma symptoms, the alveolar septa thickening and the infiltration of inflammatory cell around bronchi and bronchioles as well as reduced the levels of IgE, IL-8 and TNF-α in serum or BALF. Furthermore, GPH could inhibit the phosphorylation level of Akt and the expression of PI3K, an efficacy supported by the findings by way of Western blot which suggests that GPH in the treatment of allergic asthma was linked to PI3K/Akt signal pathway. In this study, a comprehensive strategy to combine the UPLC-Q-Orbitrap HRMS with network pharmacology was employed to clarify the mechanism of GPH against allergic asthma, a finding where GPH may inhibit PI3K/Akt signal pathway to protect mice from OVA-induced allergic asthma. This study provides a deeper understanding of the pharmacological mechanism of GPH in treatment of asthma, offering a scientific reference for further research and clinical application of GPH in terms of allergic asthma. [Display omitted] • Plasma pharmacochemistry, network pharmacology and verification were integrated to explore mechanism of GPH against asthma. • Effective compounds of GPH including arbutin, luteolin and marmesin had good binding with core targets related to PI3K/Akt pathway. • GPH might inhibit PI3K/Akt signal pathway to protect mice from OVA-induced allergic asthma in experimental verification. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract that closely related to immune dysfunction. Macrophages are the key gatekeeper of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages have been recognized as attractive targets to develop new therapeutic approaches for the disease. Recently, the growing field of immunometabolism has reinforced that metabolism reprogramming is a key determinant that dictates macrophage functions and subsequent disease progression. Herein, we elaborated how metabolic alterations underlie intestinal macrophage phenotype and function during IBD, and how microenvironmental cues trigger their metabolic reprogramming processes. More importantly, we deciphered the distinguishing characteristic of macrophage immunometabolism in IBD from other inflammatory diseases, and also summarized potential therapeutic approaches for IBD by manipulating cellular metabolism of macrophages. Finally, we discussed the major opportunities and challenges of harnessing metabolism to modulate aberrant macrophage responses in IBD. Altogether, our overview provides a framework for understanding the critical roles and potential therapeutic targets of macrophage immunometabolism in IBD. [ABSTRACT FROM AUTHOR]

• MCP ameliorates ISO-induced myocardial fibrosis and cardiac dysfunction. • MCP decreases ISO-induced IL-1β, IL-18, TNF-α and Gal-3 levels. • MCP ameliorates myocardial fibrosis via inhibiting TLR4/MyD88/NF-κB signaling. Myocardial fibrosis (MF) plays a key role in the development and progression of heart failure (HF) with limited effective therapies. Galectin-3 (Gal-3) is a biomarker associated with fibrosis and inflammation in patients with HF. The Gal-3 inhibitor modified citrus pectin (MCP) protects against cardiac dysfunction, though the underlying mechanism remains unclear. The aim of this study was to investigate the effect and mechanism of MCP on MF using an isoproterenol (ISO)-induced rat model of HF. Cardiac function was analyzed by echocardiography and electrocardiography. Histopathological changes in the heart tissue were assessed by hematoxylin-eosin and Masson trichrome staining. The mRNA and protein expression levels of signaling molecules and pro-inflammatory cytokines were monitored by immunohistochemistry, western blot, qRT-PCR and ELISA analyses. The results demonstrated that MCP ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition. Furthermore, MCP downregulated the expression of Gal-3, TLR4 and MyD88, thereby inhibiting NF-κB-p65 activation. MCP also decreased the expression of IL-1β, IL-18 and TNF-α, which have been implicated in the pathogenesis of HF. These inhibitory effects were observed on day 15 and continued until day 22. Taken together, these results suggest that MCP ameliorates cardiac dysfunction through inhibiting inflammation and MF. These effects may be through downregulating Gal-3 expression and suppressing activation of the TLR4/MyD88/NF-κB signaling pathway. The present study supports the use of Gal-3 as a therapeutic target for the treatment of MF after myocardial infarction. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat and immunoglobulin domain-containing protein 1 (LINGO-1) is a transmembrane protein that negatively regulates neural regeneration in the central nervous system. LINGO-1 expression is up-regulated after central nerve injury, and is accompanied by cell death. Both LINGO-1 and cell death in the injury microenvironment are thought to limit neural regeneration, but the relationship between LINGO-1 and cell death has not been characterized. To investigate whether LINGO-1 deletion improves the spinal cord microenvironment after spinal cord injury (SCI) and contributes to cell survival, we generated LINGO-1 knockout (KO) mice. These mice and wild-type control mice were subjected to spinal cord transection. Fourteen days after spinal cord transection, cell apoptosis, inflammation, glial scar, and growth of nerve fibers were evaluated by immunostaining. The results showed that LINGO-1 KO mice demonstrated a profound reduction in expression of caspase-3, transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL), ionized calcium binding adapter molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and chondroitin sulfate proteoglycans (CSPGs) compared to controls. In contrast, expression of neurofilament (NF) at the SCI site in LINGO-1 KO mice was markedly increased compared to that in wild-type mice. These results suggested that LINGO-1 plays a critical role in the injury microenvironment in processes such as cell death, inflammatory response, and glial scar formation. Importantly, LINGO-1 deletion and a positive microenvironment may exert synergistic effects to promote nerve fiber regeneration. Therefore, inhibition of LINGO-1 may be a therapeutic strategy to promote neural regeneration following SCI. • LINGO-1 deletion decreases cell apoptosis in the injured tissue after SCI. • LINGO-1 deletion reduces inflammation and glia scar in the injured tissue after SCI. • LINGO-1 deletion promotes nerve regeneration after complete spinal cord transection. [ABSTRACT FROM AUTHOR]