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Immunological Investigations Apr 2024Psoriasis is a chronic inflammatory disease characterized by squamous and erythematous plaques on the skin and the involvement of the immune system. Global prevalence... (Review)
Review
Psoriasis is a chronic inflammatory disease characterized by squamous and erythematous plaques on the skin and the involvement of the immune system. Global prevalence for psoriasis has been reported around 1-3% with a higher incidence in adults and similar proportions between men and women. The risk factors associated with psoriasis are both extrinsic and intrinsic, out of which a polygenic predisposition is a highlight out of the latter. Psoriasis etiology is not yet fully described, but several hypothesis have been proposed: 1) the autoimmunity hypothesis is based on the over-expression of antimicrobial peptides such as LL-37, the proteins ADAMTSL5, K17, and hsp27, or lipids synthesized by the PLA2G4D enzyme, all of which may serve as autoantigens to promote the differentiation of autoreactive lymphocytes T and unleash a chronic inflammatory response; 2) dysbiosis of skin microbiota hypothesis in psoriasis has gained relevance due to the observations of a loss of diversity and the participation of pathogenic bacteria such as spp. or spp. the fungi spp. or . and the virus HPV, HCV, or HIV in psoriatic plaques; 3) the oxidative stress hypothesis, the most recent one, describes that the cell injury and the release of proinflammatory mediators and antimicrobial peptides that leads to activate of the Th1/Th17 axis observed in psoriasis is caused by a higher release of reactive oxygen species and the imbalance between oxidant and antioxidant mechanisms. This review aims to describe the mechanisms involved in the three hypotheses on the etiopathogeneses of psoriasis.
Topics: Male; Adult; Female; Humans; Psoriasis; Skin; Autoimmunity; Autoantigens; Antimicrobial Peptides; ADAMTS Proteins
PubMed: 38240030
DOI: 10.1080/08820139.2024.2302823 -
Aktuelle Urologie Feb 2024
Topics: Humans; Botulinum Toxins, Type A; Urinary Bladder, Overactive
PubMed: 38330951
DOI: 10.1055/a-2056-2793 -
European Review For Medical and... Aug 2023The aim of this study was to investigate the protective effect and mechanism of action (MOA) of Qiliqiangxin capsule (QL) in the deoxycorticosterone acetate (DOCA)...
OBJECTIVE
The aim of this study was to investigate the protective effect and mechanism of action (MOA) of Qiliqiangxin capsule (QL) in the deoxycorticosterone acetate (DOCA) salt-induced rat heart failure with preserved ejection fraction (HFpEF) model.
MATERIALS AND METHODS
Nono-nephrectomy sixty Sprague Dawley (SD) rats received DOCA salt injection and 1% saline in drinking water for 4 weeks and were randomly divided into four groups on average: Model group (n=15), Sac/Val group (Sacubitril Valsartan 0.02 g/kg, n=15), QL-L group (Qiliqiangxin 0.25 g/kg, n=15) and QL-H group (Qiliqiangxin 1 g/kg, n=15). Another Normal group was set (n=15). Blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac index, echocardiography, and hemodynamics were measured to evaluate heart function. Masson and Wheat germ agglutinin (WGA) staining was performed to observe the fibrosis deposition and the cross-sectional area (CSA) of cardiomyocytes. The concentration levels of the serum cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and IL-10 inflammatory factors, were detected by ELISA; matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), transforming growth factor-β1 (TGF-β1), nuclear factor-κB (NF-κB), Smad homologue 2 (Smad2) and Smad homologue 3 (Smad3) expression were detected by Western-blot.
RESULTS
Compared with the Model group, QL treatment significantly ameliorated the heart function in DOCA salt-induced rat HFpEF model, showing a decrease in cardiac index, an increase of the EF and E/A ratio, a reduction in the left ventricular anterior/posterior wall (LVAW/LVPW), in the time contraction of isovolumic diastolic time (IVRT), -dP/dt Max, and Tau, and the decrease of serum NT-ProBNP. Masson and WGA staining indicated that QL inhibited the fibrosis deposition and the myocardial hypertrophy compared with the Model group, which was consistent in reducing the protein expression levels of cardiac remodeling such as TGF-β1, MMP2, MMP9, Smad2, and Smad3. Moreover, QL treatment inhibited the expression of NF-κB in the heart tissues and decreased the serum concentration of pro-inflammatory cytokines TNF-α and IL-2, instead, increasing the IL-10 concentration.
CONCLUSIONS
QL improved the cardiac function and inhibited the myocardial fibrosis in DOCA salt-induced rat HFpEF by improving diastolic dysfunction, preventing left ventricular hypertrophy, and ameliorating the inflammatory responses model in DOCA salt-induced rat HFpEF model.
Topics: Rats; Animals; Matrix Metalloproteinase 2; Interleukin-10; Desoxycorticosterone Acetate; Matrix Metalloproteinase 9; Transforming Growth Factor beta1; Heart Failure; NF-kappa B; Tumor Necrosis Factor-alpha; Ventricular Remodeling; Rats, Sprague-Dawley; Stroke Volume; Myocytes, Cardiac; Cytokines
PubMed: 37606135
DOI: 10.26355/eurrev_202308_33298 -
Journal of Periodontology Nov 2023Resolvins are endogenous mediators of the resolution of inflammation. They are derived from omega-3 polyunsaturated fatty acid precursors. Resolvin D1 (RvD1) and...
BACKGROUND
Resolvins are endogenous mediators of the resolution of inflammation. They are derived from omega-3 polyunsaturated fatty acid precursors. Resolvin D1 (RvD1) and Resolvin E1 (RvE1) are the best-characterized members for actively promoting periodontal regeneration in experimental animal models. Here, we evaluated the efficacy of RvD1 and RvE1 on cementoblasts, the key cells involved in dental cementum regeneration and the attachment of the tooth to the alveolar bone.
METHODS
Immortalized mouse cementoblasts (OCCM-30) were treated with different concentrations (0.1-1000 ng/mL) of RvD1 and RvE1. Cell proliferation was measured using an electrical impedance-based real-time cell analyzer. Mineralization was evaluated with von Kossa staining. The mRNA expression of mineralized tissue-associated markers of bone sialoprotein (BSP), Type I collagen (COL I), osteocalcin (OCN), osteopontin (OPN), runt-related transcription factor 2 (RunX2), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (NF-κB) (RANK), receptor activator of NF-κB ligand (RANKL), and extracellular matrix-degrading enzymes [matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, and their tissue inhibitors (TIMP-1, TIMP-2)], RvE1 receptor (ChemR23) and RvD1 receptor (ALX/PFR2), cytokines (tumor necrosis factor-alpha {TNF-α}, interleukin {IL}-1β, IL-6, IL-8, IL-10, IL-17), oxidative stress enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPX), and cyclooxygenase-2 (Cox-2)] were analyzed using quantitative polymerase chain reaction (qPCR).
RESULTS
Both RvD1 and RvE1 (10-100 ng/mL) significantly increased the proliferation of cementoblasts and mineralized nodules at all concentrations (p < 0.05). RvE1 increased BSP, RunX2, and ALP compared with the RvD1 dose and time-dependently, while RvD1 and RvE1 differentially regulated COL-I. RvE1 increased OPG mRNA expression, whereas RANK-RANKL mRNA expression decreased by RvE1. MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 expressions were reduced by RvE1 compared with RvD1. Treatment of cementoblasts with RvD1 and RvE1 differentially affected cytokine and oxidative stress enzymes while significantly increasing their receptor expressions (ChemR23 and ALX/PFR2).
CONCLUSIONS
RvD1 and RvE1 regulate proliferation, mineralization, and gene expression in cementoblasts using similar pathways while differentially affecting tissue degradation, suggesting a targeted therapeutic approach for cementum turnover during periodontal regeneration.
Topics: Mice; Animals; Dental Cementum; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-1; Matrix Metalloproteinase 3; Core Binding Factor Alpha 1 Subunit; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Integrin-Binding Sialoprotein; RNA, Messenger; Docosahexaenoic Acids; Eicosapentaenoic Acid
PubMed: 37322861
DOI: 10.1002/JPER.22-0510 -
PloS One 2023Patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer (BRCA) than the general population. In this study, we explored the underlying...
BACKGROUND
Patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer (BRCA) than the general population. In this study, we explored the underlying molecular mechanism that is dysregulated in both diseases.
METHODS
Weighted gene coexpression network analysis (WGCNA) was executed with the SLE and BRCA datasets from the Gene Expression Omnibus (GEO) website and identified the potential role of membrane metalloendopeptidase (MME) in both diseases. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of related proteins and miRNAs were performed to investigate the potential molecular pathways.
RESULTS
WGCNA revealed that MME was positively related to SLE but negatively related to BRCA. In BRCA, MME expression was significantly decreased in tumor tissues, especially in luminal B and infiltrating ductal carcinoma subtypes. Receiver operating characteristic (ROC) analysis identified MME as a valuable diagnostic biomarker of BRCA, with an area under the curve (AUC) value equal to 0.984 (95% confidence interval = 0.976-0.992). KEGG enrichment analysis suggested that MME-related proteins and targeted miRNAs may reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway. Low MME expression was associated with favorable relapse-free survival (RFS) but no other clinical outcomes and may contribute to resistance to chemotherapy in BRCA, with an AUC equal to 0.527 (P value < 0.05).
CONCLUSIONS
In summary, MME expression was significantly decreased in BRCA but positively correlated with SLE, and it might reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway.
Topics: Female; Humans; Breast Neoplasms; Lupus Erythematosus, Systemic; MicroRNAs; Neprilysin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PubMed: 37585411
DOI: 10.1371/journal.pone.0289960 -
World Journal of Urology May 2024To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high... (Review)
Review
PURPOSE
To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease.
METHODS
A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic.
RESULTS
Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified.
CONCLUSIONS
Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.
Topics: Penile Induration; Humans; Male; Conservative Treatment; Extracorporeal Shockwave Therapy; Phosphodiesterase 5 Inhibitors; Traction; Hyaluronic Acid; Microbial Collagenase; Practice Guidelines as Topic
PubMed: 38740620
DOI: 10.1007/s00345-024-04975-6 -
Liver International : Official Journal... Jan 2024We have previously shown in a model of hepatic ischaemia/reperfusion injury that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) restores...
BACKGROUND AND AIMS
We have previously shown in a model of hepatic ischaemia/reperfusion injury that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) restores reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), an inverse modulator of metalloproteases (MMPs) and inhibitor of the sheddases ADAM10 and ADAM17 involved in inflammation and fibrogenesis. Here, the effects of FXR agonists OCA and INT-787 on hepatic levels of RECK, MMPs, ADAM10 and ADAM17 were compared in a diet-induced ob/ob mouse model of non-alcoholic steatohepatitis (NASH).
METHODS
Lep ob/ob NASH mice fed a high-fat diet (HFD) or control diet (CD) for 9 weeks (wks) were treated with OCA or INT-787 0.05% dosed via HFD admixture (30 mg/kg/day) or HFD for further 12 wks. Serum alanine transaminase (ALT) and inflammatory cytokines, liver RECK, MMP-2 and MMP-9 activity as well as ADAM10, ADAM17, collagen deposition (Sirius red), hepatic stellate cell activation (α-SMA) and pCK reactive biliary cells were quantified.
RESULTS
Only INT-787 significantly reduced serum ALT, IL-1β and TGF-β. A downregulation of RECK expression and protein levels observed in HFD groups (at 9 and 21 wks) was counteracted by both OCA and INT-787. HFD induced a significant increase in liver MMP-2 and MMP-9; OCA administration reduced both MMP-2 and MMP-9 while INT-787 markedly reduced MMP-2 expression. OCA and INT-787 reduced both ADAM10 and ADAM17 expression and number of pCK cells. INT-787 was superior to OCA in decreasing collagen deposition and α-SMA levels.
CONCLUSION
INT-787 is superior to OCA in controlling specific cell types and clinically relevant anti-inflammatory and antifibrotic molecular mechanisms in NASH.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Liver; Chenodeoxycholic Acid; Inflammation; Diet, High-Fat; Collagen
PubMed: 37904642
DOI: 10.1111/liv.15767 -
Chemico-biological Interactions Jan 2024Osteoarthritis (OA) is a common joint degenerative disease, and chondrocyte injury is the main pathological and physiological change. Ruscogenin (Rus), a bioactive...
Osteoarthritis (OA) is a common joint degenerative disease, and chondrocyte injury is the main pathological and physiological change. Ruscogenin (Rus), a bioactive compound isolated from Radix Ophiopogon japonicus, exhibits various pharmacological effects. The aim of this research was to test the role and mechanism of Rus on OA both in vivo and in vitro. Destabilized medial meniscus (DMM)-induced OA model was established in vivo and IL-1β-stimulated mouse chondrocytes was used to explore the role of Rus on OA in vitro. In vivo, Rus exhibited protective effects against DMM-induced OA model. Rus could inhibit MMP1 and MMP3 expression in OA mice. In vitro, IL-1β-induced inflammation and degradation of extracellular matrix were inhibited by Rus, as confirmed by the inhibition of PGE2, NO, MMP1, and MMP3 by Rus. Also, IL-1β-induced ferroptosis was suppressed by Rus, as confirmed by the inhibition of MDA, iron, and ROS, as well as the upregulation of GSH, GPX4, Ferritin, Nrf2, and SLC7A11 expression induced by Rus. Furthermore, the suppression of Rus on IL-1β-induced inflammation, MMPs production, and ferroptosis were reversed when Nrf2 was knockdown. In conclusion, Rus attenuated OA progression through inhibiting chondrocyte ferroptosis via Nrf2/SLC7A11/GPX4 signaling pathway.
Topics: Animals; Mice; Cartilage; Chondrocytes; Ferroptosis; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; NF-E2-Related Factor 2; Osteoarthritis; Signal Transduction; Spirostans
PubMed: 38122922
DOI: 10.1016/j.cbi.2023.110835 -
Dermatologic Clinics Jan 2024Botulinum toxin A (BT) is the most required treatment in face rejuvenation. However, applications of BT on the lower third are off-label and specific tips for the... (Review)
Review
Botulinum toxin A (BT) is the most required treatment in face rejuvenation. However, applications of BT on the lower third are off-label and specific tips for the treatment of this area should be taken into account to achieve best results. In the current study, literature concerning BT treatment of lower face has been revised and summarized according to anatomy and indications, tips, and complications. BT treatment of the lower face has been reported to be effective and safe when performed with adequate knowledge of anatomy and techniques.
Topics: Humans; Neurotoxins; Cosmetic Techniques; Botulinum Toxins, Type A; Rejuvenation; Neuromuscular Agents
PubMed: 37977685
DOI: 10.1016/j.det.2023.06.002 -
Science Advances Jul 2023The gelatinases, matrix metalloproteinase 2 (MMP-2) and MMP-9, are key for leukocyte penetration of the brain parenchymal border in neuroinflammation and the functional...
The gelatinases, matrix metalloproteinase 2 (MMP-2) and MMP-9, are key for leukocyte penetration of the brain parenchymal border in neuroinflammation and the functional integrity of this barrier; however, it is unclear which MMP substrates are involved. Using a tailored, sensitive, label-free mass spectrometry-based secretome approach, not previously applied to nonimmune cells, we identified 119 MMP-9 and 21 MMP-2 potential substrates at the cell surface of primary astrocytes, including known substrates (β-dystroglycan) and a broad spectrum of previously unknown MMP-dependent events involved in cell-cell and cell-matrix interactions. Using neuroinflammation as a model of assessing compromised astroglial barrier function, a selection of the potential MMP substrates were confirmed in vivo and verified in human samples, including vascular cell adhesion molecule-1 and neuronal cell adhesion molecule. We provide a unique resource of potential MMP-2/MMP-9 substrates specific for the astroglia barrier. Our data support a role for the gelatinases in the formation and maintenance of this barrier but also in astrocyte-neuron interactions.
Topics: Humans; Gelatinases; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Blood-Brain Barrier; Astrocytes; Neuroinflammatory Diseases
PubMed: 37467333
DOI: 10.1126/sciadv.adg0686