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Noise & HealthPresbycusis can be mediated by the effects of inflammatory processes on the auditory system, and these aging biological mechanisms remain poorly studied.
CONTEXT
Presbycusis can be mediated by the effects of inflammatory processes on the auditory system, and these aging biological mechanisms remain poorly studied.
AIMS
The aim of this study was to determine whether plasma biomarkers are associated with hearing disorders caused by aging in the elderly.
SETTINGS AND DESIGN
Cross-sectional study with 106 participants in the Active Aging Project, 93 (88%) females and 13 (12%) males, with an average age of 70 years.
METHODS AND MATERIAL
Audiological evaluation was performed with pure tone audiometry and collection of peripheral blood for the measurement of plasma levels of interleukins 2, 4, 6, and 10, tumor necrosis factor-α, and interferon-γ by means of flow cytometry.
STATISTICAL ANALYSIS USED
The SPSS (v.0, SPSS Inc., Chicago, USA) was used for the analysis of the data obtained. For all data analyzed, the significance level adopted was P < 0.05 and 95% confidence interval.
RESULTS
There were statistically significant correlations between male and IL-2 (P = 0.031; rs = 0.210), mean II of the right ear (P = 0.004; rs = 0.279), longer in years (P = 0.002; rs = 0.307) and in hours (P = 0.004; rs = 0.281) of noise exposure also in males.
CONCLUSIONS
In the present study, there was an association between the male gender and higher plasma levels of IL-2, an increase in the average hearing in the right ear, and greater time in years and hours of exposure to noise. There was a predominance of mild sensorineural hearing loss and worsening of hearing related to age, characteristics of presbycusis.
Topics: Humans; Male; Female; Aged; Cross-Sectional Studies; Interleukin-2; Audiometry, Pure-Tone; Biomarkers; Presbycusis; Tumor Necrosis Factor-alpha; Interferon-gamma; Middle Aged; Aged, 80 and over; Aging
PubMed: 38904818
DOI: 10.4103/nah.nah_3_23 -
Archives of Dermatological Research Jun 2024Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat...
Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat acne. We conducted experiments to quantitatively assess the effects of CBD on acne-related cellular pathways. SEB-1 sebocytes and HaCaT keratinocytes were exposed to various CBD concentrations. CBD exhibited a concentration-dependent impact on cell viability and notably reduced SEB-1 viability; furthermore, it induced apoptosis and a significant increase in the apoptotic area at higher concentrations. Additionally, CBD remarkably reduced pro-inflammatory cytokines, including CXCL8, IL-1α, and IL-1β. Additionally, it inhibited lipid synthesis by modulating the AMPK-SREBP-1 pathway and effectively reduced hyperkeratinization-related protein keratin 16. Simultaneously, CBD stimulated the synthesis of elastin, collagen 1, and collagen 3. These findings emphasize the potential of CBD for the management of acne because of its anti-inflammatory, apoptotic, and lipid-inhibitory effects. Notably, the modulation of the Akt/AMPK-SREBP-1 pathway revealed a novel and promising mechanism that could address the pathogenesis of acne.
Topics: Humans; Acne Vulgaris; Cannabidiol; Apoptosis; Keratinocytes; Cell Survival; Signal Transduction; Cicatrix; Anti-Inflammatory Agents; Sterol Regulatory Element Binding Protein 1; HaCaT Cells; AMP-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Collagen Type I; Collagen Type III; Elastin; Sebaceous Glands; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Cell Line
PubMed: 38904694
DOI: 10.1007/s00403-024-03131-9 -
International Journal of Biological... 2024Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a...
Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice ( ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.
Topics: Animals; Dermatitis, Atopic; Langerhans Cells; Mice; Cell Movement; Mice, Knockout; Interleukin-1; Keratinocytes; Dinitrofluorobenzene; NF-kappa B; Interleukins
PubMed: 38904012
DOI: 10.7150/ijbs.93843 -
International Journal of Medical... 2024Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study...
Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Analysis of the GSE13159 database revealed that , () within the TXNIP/NLRP3 pathway were significantly upregulated and () was downregulated in AML patients (, = 0.031; , = 0.042; , = 0.038). Compared to high expression, AML patients with low expression had a longer overall survival (OS) in the GSE12417 dataset ( = 0.004). Moreover, both the training and validation results indicated that lower , , and expression were associated with favorable prognosis (GSE12417, = 0.009; TCGA, = 0.050; JNU, = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using // genes in novel targeted therapies for AML.
Topics: Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Leukemia, Myeloid, Acute; Carrier Proteins; Female; Male; Prognosis; Biomarkers, Tumor; Middle Aged; Interleukin-1beta; Inflammasomes; Signal Transduction; Adult; Aged; Gene Expression Regulation, Leukemic; Thioredoxins
PubMed: 38903927
DOI: 10.7150/ijms.96627 -
International Journal of Medical... 2024Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against...
Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca(PO)) , which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
Topics: Animals; Aortic Aneurysm, Abdominal; Apoptosis; Mice; Glutamine; Angiotensin II; Macrophage Activation; Muscle, Smooth, Vascular; Humans; Myocytes, Smooth Muscle; Oxidative Stress; Reactive Oxygen Species; Disease Models, Animal; Male; Macrophages; Aorta, Abdominal; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Tumor Necrosis Factor-alpha; Interleukin-6; Calcium Phosphates
PubMed: 38903916
DOI: 10.7150/ijms.96395 -
BMC Immunology Jun 2024Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.
OBJECTIVES
This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.
MATERIALS AND METHODS
A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.
RESULTS
Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.
CONCLUSIONS
Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.
Topics: Arthritis, Rheumatoid; Humans; MicroRNAs; Cell Proliferation; Cell Movement; Tumor Necrosis Factor-alpha; Male; Middle Aged; Female; Cell Line; Up-Regulation; Biomarkers; Inflammation; Synovial Membrane; Adult; Aged
PubMed: 38902605
DOI: 10.1186/s12865-024-00629-9 -
Scientific Reports Jun 2024Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate...
Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Middle Aged; Registries; Adult; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Age of Onset; Antirheumatic Agents; Tumor Necrosis Factor-alpha
PubMed: 38902436
DOI: 10.1038/s41598-024-65180-4 -
Scientific Reports Jun 2024The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to...
The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.
Topics: Colitis, Ulcerative; Drugs, Chinese Herbal; Humans; Molecular Docking Simulation; Network Pharmacology; Protein Interaction Maps; Proto-Oncogene Proteins c-akt; Interleukin-6; Quercetin; Interleukin-1beta
PubMed: 38902425
DOI: 10.1038/s41598-024-64683-4 -
Veterinaria Italiana Mar 2024The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether...
The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether there are any changes in TNF-α concentration and their dependence during therapy for heartworm disease (HWD). For this study, 14 client-owned dogs with HWD were selected. Clinical and parasitological examinations (modified Knott test for circulating microfilariae and SNAP Test IDEXX for circulating D. immitis antigen) had been used for diagnosing D. immitis and HWD. All dogs were treated with an alternative therapy for HWD (oral doxycycline 10 mg/kg b.w., once daily for 6 weeks, then alternately 4 weeks without and 2 weeks with the medication, and oral ivermectin 6-14 µg/kg b.w., every 2 weeks). The dogs blood sera at the moment of HWD diagnosis, during and at the end of therapy were frozen for further quantifying of TNF-α (Canine TNF-alpha ELISA kit, Thermo scientific). At the moment of HWD diagnosis TNF-α was detected in 9 dogs (7.21±12.44 pg/ml). Concentration of TNF-α was not significantly change during the therapy, neither related to the level of D. immitis antigen nor to antigen level changes. The alternative therapy for HWD has no influence on TNF-α concentration dynamics.
Topics: Animals; Dogs; Dirofilariasis; Dog Diseases; Tumor Necrosis Factor-alpha; Dirofilaria immitis; Male; Female; Doxycycline; Ivermectin
PubMed: 38898794
DOI: 10.12834/VetIt.2662.22847.2 -
Journal of Cellular and Molecular... Jun 2024Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential...
Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.
Topics: Animals; Exosomes; Mesenchymal Stem Cells; Female; Tumor Necrosis Factor-alpha; Rats; Humans; Pelvic Organ Prolapse; Matrix Metalloproteinase 2; Rats, Sprague-Dawley; Interleukin-6; Pelvic Floor; Disease Models, Animal; Bone Marrow Cells; Vagina; Mesenchymal Stem Cell Transplantation; Pelvic Floor Disorders; Middle Aged
PubMed: 38898783
DOI: 10.1111/jcmm.18451