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Nutrition & Diabetes Jun 2024Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of...
BACKGROUND/OBJECTIVES
Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in "adiponectin paradox", we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation.
METHODS
This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α.
RESULTS
This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036-0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (P < 0.001 and P < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03-0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5-49.2, P = 0.02).
CONCLUSIONS
In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.
Topics: Humans; Adiponectin; Male; Fatty Acids, Nonesterified; Female; Middle Aged; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Adult; Inflammation
PubMed: 38886355
DOI: 10.1038/s41387-024-00302-5 -
PloS One 2024Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic...
Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.
Topics: Animals; Matrix Metalloproteinase 9; Dry Eye Syndromes; Gastrointestinal Microbiome; Mice; NF-kappa B; Probiotics; Signal Transduction; Mice, Inbred C57BL; Tears; Fecal Microbiota Transplantation; Tumor Necrosis Factor-alpha; Conjunctiva
PubMed: 38885258
DOI: 10.1371/journal.pone.0303423 -
European Review For Medical and... Jun 2024Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several... (Observational Study)
Observational Study
OBJECTIVE
Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1β, and Il-10 serum levels.
PATIENTS AND METHODS
This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery.
RESULTS
Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1β and IL-10 peak levels were reached with a time-course pattern similar to proNGF.
CONCLUSIONS
Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.
Topics: Humans; Nerve Growth Factor; Burns; Child; Prospective Studies; Female; Male; Child, Preschool; Interleukins; Interleukin-1beta; Interleukin-10; Infant; Protein Precursors
PubMed: 38884514
DOI: 10.26355/eurrev_202406_36385 -
Frontiers in Immunology 2024Sepsis is a life-threatening inflammatory condition caused by dysregulated host responses to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a...
INTRODUCTION
Sepsis is a life-threatening inflammatory condition caused by dysregulated host responses to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that causes inflammation and organ injury in sepsis. Kupffer cells can be activated and polarized to the inflammatory M1 phenotype, contributing to tissue damage by producing proinflammatory mediators. We hypothesized that eCIRP promotes Kupffer cell M1 polarization in sepsis.
METHODS
We stimulated Kupffer cells isolated from wild-type (WT) and TLR4 mice with recombinant mouse (rm) CIRP (i.e., eCIRP) and assessed supernatant IL-6 and TNFα levels by ELISA. The mRNA expression of iNOS and CD206 for M1 and M2 markers, respectively, was assessed by qPCR. We induced sepsis in WT and CIRP mice by cecal ligation and puncture (CLP) and assessed iNOS and CD206 expression in Kupffer cells by flow cytometry.
RESULTS
eCIRP dose- and time-dependently increased IL-6 and TNFα release from WT Kupffer cells. In TLR4 Kupffer cells, their increase after eCIRP stimulation was prevented. eCIRP significantly increased iNOS gene expression, while it did not alter CD206 expression in WT Kupffer cells. In TLR4 Kupffer cells, however, iNOS expression was significantly decreased compared with WT Kupffer cells after eCIRP stimulation. iNOS expression in Kupffer cells was significantly increased at 20 h after CLP in WT mice. In contrast, Kupffer cell iNOS expression in CIRP mice was significantly decreased compared with WT mice after CLP. CD206 expression in Kupffer cells was not different across all groups. Kupffer cell M1/M2 ratio was significantly increased in WT septic mice, while it was significantly decreased in CIRP mice compared to WT mice after CLP.
CONCLUSION
Our data have clearly shown that eCIRP induces Kupffer cell M1 polarization via TLR4 pathway in sepsis, resulting in overproduction of inflammatory cytokines. eCIRP could be a promising therapeutic target to attenuate inflammation by preventing Kupffer cell M1 polarization in sepsis.
Topics: Animals; Kupffer Cells; Sepsis; Mice; Mice, Knockout; RNA-Binding Proteins; Mice, Inbred C57BL; Toll-Like Receptor 4; Male; Nitric Oxide Synthase Type II; Disease Models, Animal; Inflammation; Tumor Necrosis Factor-alpha; Mannose Receptor; Interleukin-6
PubMed: 38881891
DOI: 10.3389/fimmu.2024.1411930 -
Biochemistry. Biokhimiia May 2024Tumor necrosis factor (TNF) is one of many cytokines - protein molecules responsible for communication between the cells of immune system. TNF was discovered and given... (Review)
Review
Tumor necrosis factor (TNF) is one of many cytokines - protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses "man-made" mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.
Topics: Animals; Humans; Tumor Necrosis Factor-alpha; Mice; Gene Editing; Neoplasms
PubMed: 38880646
DOI: 10.1134/S0006297924050067 -
Medicine Jun 2024To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the...
To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease. This was a single-center retrospective study. 180 patients with dental pulp disease were divided into AH Plus group (n = 60), GuttaFlow group (n = 60) and iRoot SP group (n = 60) according to the different treatment methods. Patients in different groups were treated with corresponding root canal sealant combined with warm gutta-percha vertical compression technique. The quality of root canal filling, filling time, filling area ratio, the incidence of pain after operation, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and efficacy at 6 months after operation were compared among the 3 groups, respectively. The filling time in the GuttaFlow group and the iRoot SP group was significantly shorter than that in the AH Plus group (P < .001). There were significant differences in pain grade (P = .015) and pain rate (P = .016) among the 3 groups, and the pain rate in the GuttaFlow group and the iRoot SP group was significantly lower than that in the AH Plus group (P = .016). The time-point effect, intergroup effect and time-groups effect of serum TNF-α and IL-6 were significantly different (P < .001), and the levels of the 3 groups after treatment were significantly lower than those before treatment (P < .05), and the levels were significantly lower in the GuttaFlow group and the iRoot SP group (P < .05). There were significant differences in efficacy grading and effective rate among the 3 groups (P = .028), and the effective rate of iRoot SP group was significantly higher than that of AH Plus group (P < .05). The iRoot SP or GuttaFlow as root canal sealant combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease is better than AH Plus, and the former one can shorten the filling time, relieve the postoperative pain and improve the inflammatory response, but the long-term apical sealing effect of iRoot SP is better than GuttaFlow.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Root Canal Filling Materials; Gutta-Percha; Dental Pulp Diseases; Interleukin-6; Middle Aged; Tumor Necrosis Factor-alpha; Treatment Outcome; Young Adult; Drug Combinations; Dimethylpolysiloxanes
PubMed: 38875398
DOI: 10.1097/MD.0000000000038414 -
Science Advances Jun 2024Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign...
Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign body response. In other fibrotic disorders, a fibroblast subpopulation defined by Thy-1 loss is strongly correlated with fibrosis yet we do not know what promotes Thy-1 loss. We have previously shown that Thy-1 is an integrin regulator enabling normal fibroblast mechanosensing, and here, leveraging nonfibrotic microporous annealed particle (MAP) hydrogels versus classical fibrotic bulk hydrogels, we demonstrate that mice mount a fibrotic response to MAP gels that includes inflammatory signaling. We found that a distinct and cryptic α-smooth muscle actin-positive Thy-1 fibroblast population emerges in response to interleuklin-1β (IL-1β) and tumor necrosis factor-α (TNFα). Furthermore, IL-1β/TNFα-induced Thy-1 fibroblasts consist of two distinct subpopulations that are strongly proinflammatory. These findings illustrate the emergence of a unique proinflammatory, profibrotic fibroblast subpopulation that is central to fibrotic encapsulation of biomaterials.
Topics: Animals; Mice; Biocompatible Materials; Fibroblasts; Fibrosis; Hydrogels; Interleukin-1beta; Mice, Knockout; Thy-1 Antigens; Tumor Necrosis Factor-alpha
PubMed: 38875340
DOI: 10.1126/sciadv.adf2675 -
European Journal of Sport Science Jul 2024This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes-specific markers and inflammation in women with type 2 diabetes: A randomized double-blind placebo-controlled trial.
This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.
Topics: Humans; Female; Diabetes Mellitus, Type 2; Crocus; Double-Blind Method; Middle Aged; Insulin Resistance; Dietary Supplements; Biomarkers; Exercise; Inflammation; Interleukin-6; Obesity; Blood Glucose; Tumor Necrosis Factor-alpha; Hemostasis
PubMed: 38874882
DOI: 10.1002/ejsc.12125 -
International Journal of Implant... Jun 2024This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.
PURPOSE
This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.
METHODS
A cohort of 29 patients with a total of 76 implants was included in this study and subsequently divided into three groups based on peri-implant clinical parameters and radiographic examination: healthy (peri-implant health) (n = 29), mucositis (n = 22), and peri-implantitis (n = 25) groups. The levels of ET-1 (ρg/site) and interleukin (IL)-1β (ρg/site) in peri-implant sulcus fluid (PISF) samples were determined using enzyme immunoassay. Statistical analyses were conducted using Kruskal-Wallis and Steel-Dwass tests. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of the biomarkers.
RESULTS
ET-1 levels were significantly elevated in the peri-implantitis group compared to those in the healthy group, and were highest in the peri-implant mucositis group. Additionally, IL-1β levels were significantly higher in the peri-implantitis group than those in the healthy group. ROC curve analysis indicated that ET-1 exhibited superior area under the curve values, sensitivity, and specificity compared to those of IL-1β.
CONCLUSIONS
Our findings suggest that the presence of ET-1 in PISF plays a role in peri-implant diseases. Its significantly increased expression in peri-implant mucositis indicates its potential for enabling earlier and more accurate assessments of peri-implant inflammation when combined with conventional examination methods.
Topics: Humans; Endothelin-1; Peri-Implantitis; Cross-Sectional Studies; Male; Female; Biomarkers; Middle Aged; Interleukin-1beta; Dental Implants; Adult; Mucositis; Gingival Crevicular Fluid; Aged; ROC Curve
PubMed: 38874661
DOI: 10.1186/s40729-024-00551-0 -
CNS Neuroscience & Therapeutics Jun 2024Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized...
Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1 transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1β/NF-κB pathways.
AIM
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated.
METHODS
A-1 at 33.3 mg/kg was administrated in SOD1 transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit.
RESULTS
A-1 administration in SOD1 mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1β, pIκBα/IκBα, and pNF-κB/NF-κB.
CONCLUSIONS
A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1β/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.
Topics: Animals; Mice, Transgenic; Sirtuin 1; Mice; NF-kappa B; AMP-Activated Protein Kinases; Furans; Amyotrophic Lateral Sclerosis; Interleukin-1beta; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Lignans; Signal Transduction; Superoxide Dismutase-1; Male; Motor Neurons; Spinal Cord
PubMed: 38872258
DOI: 10.1111/cns.14692