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Purpose The purpose of this study was to compare the modulation effects of Microcurrent Therapy (MT) and Low-Level Laser Therapy (LLLT) on Matrix Metalloproteinases (MMPs) and tissue inhibitors of Metalloproteinases (TIMPs) expressions during healing of surgical wounds using appendectomy wound as a model. Methods Ninety patients who recently underwent appendectomy were randomly divided into 3 main groups of equal numbers. All cases in the three groups received ordinary medical therapy. Moreover, group A (MT group) received Microcurrent Therapy for 20 min. In addition to a designed physical therapy treatment protocol for 20 min. Group B (LLLT group) received Low-Level Laser Therapy for 20 min., plus the same designed physical therapy treatment protocol for 20 min. Group C (placebo group) received placebo shame LLLT for 20 min. plus the same designed physical therapy treatment protocol for 20 min. Enzyme-linked immunosorbent assay (ELISA) and Western Blot Technique (WBT) were used to determine expression levels of MMP-8, MMP-9, and TIMP-1 at the beginning of treatment and after the end of twelve successive sessions. Results Following therapies, results showed a statistically significant decrease in the MMP-8 and MMP-9 expressions with significantly increased expression levels of TIMP-1 in each group separately ( P  < 0.05). These changes in the expression levels towards proper healing of surgical wounds were more obvious in MT and LLLT groups compared to the placebo group, with significantly better effect in the LLLT group compared to the MT group . Conclusion Microcurrent therapy and low-level laser therapy have a notable impact in improving wound healing process as they can significantly affect the expression levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases towards good prognosis of healing process and decreasing possible wound healing complication, with superior effect of low-level laser therapy.

Background Matrix metalloproteinases (MMPs) are critical enzymes involved in the remodeling and defense mechanisms of dental pulp tissue. While their role in permanent teeth has been extensively studied, research focusing on MMPs in primary teeth remains limited. This gap highlights the need for further investigations to understand the specific contributions of MMPs to pulpal defense in primary teeth. Moreover, the clinical efficacy of Biodentine as a pulpotomy material in primary teeth warrants further exploration through well-designed studies to establish its success and long-term outcomes in pediatric dentistry. Aim This study aims to compare the expression levels of MMP-2, MMP-8, and MMP-9 in cases of reversible and irreversible pulpitis. Additionally, it seeks to evaluate the clinical success of Mineral Trioxide Aggregate (MTA) and Biodentine when used as pulpotomy agents in primary molars. By analyzing the differential expression of these MMPs, the study will contribute to a better understanding of their role in pulpal inflammation and the potential therapeutic outcomes of MTA and Biodentine in primary molars. Design In this parallel randomized controlled trial, 63 mandibular primary second molars were assigned to two main groups: Group 1, consisting of 42 teeth diagnosed with reversible pulpitis, and Group 2, consisting of 21 teeth diagnosed with irreversible pulpitis. Group 1 was further divided into two randomized subgroups, each containing 21 teeth. The expression levels of MMP-2, MMP-8, and MMP-9 were evaluated in all samples. Pulpotomy treatments were performed using MTA and Biodentine in Group 1. Clinical and radiographic evaluations were conducted over an 18-month follow-up period. Statistical analyses were carried out using The Kolmogorov-Smirnov test, t-test and Fisher’s exact test ( p  < 0.05). Results The study revealed that MMP-2 and MMP-9 expression levels were significantly elevated in specimens with irreversible pulpitis ( p  = 0.01), indicating a potential correlation between these matrix metalloproteinases and the severity of pulpal inflammation. However, no significant difference was observed in the clinical success rates of pulpotomies performed with MTA and Biodentine, suggesting that both materials are equally effective in the treatment of primary molars with reversible pulpitis. Conclusions The expression of MMP-2 and MMP-9 in pulpal blood presents a promising biomarker for assessing the degree of pulpal inflammation in primary teeth, offering a potentially valuable diagnostic tool. Additionally, the clinical success of Biodentine in pulpotomy procedures supports its viability as an effective alternative to MTA, providing a reliable option. Clinical Trial Registration ID The study protocol has been registered with an ID: NCT05145686. Registration Date: 9th November 2021.

To observe the therapeutic effects of bracketless and invisible orthodontic treatment on periodontitis, as well as on gingival crevicular fluid and serum interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and tumors. The impact of necrosis factor-alpha (TNF-α) levels fills the current knowledge gap regarding the impact of different orthodontic treatment modalities on biomarker levels in periodontitis patients. 100 patients with malocclusion secondary to periodontitis were selected as subjects.They were divided into a control group (n=50) and a study group (n=50) according to the random number method. The control group was treated with a straight wire appliances, and the study group was given bracketless and invisible orthodontic treatment. Clinical effects, Periodontal indicators [plaque index (PLI), gingival crevicular bleeding index (SBI), gingival index (GI), periodontal pocket probe depth (PD), clinical attachment loss (CAL)], gingival crevicular fluid and serum IL-6, MMP-8 and TNF-α levels and the incidence of adverse reactions were compared between the two groups. The uniqueness of this method is that it compares the impact of traditional straight-wire orthodontic treatment and invisible orthodontic treatment without brackets on biomarker levels and clinical effects in patients with periodontitis. In order to understand the role of orthodontic treatment methods in Provides useful information for use in periodontitis treatment. The main findings of this study highlight the significant impact of bracketless clear braces in improving periodontal indicators and cytokine levels. Patients treated with bracketless clear braces demonstrate better clinical outcomes in periodontitis treatment compared with traditional straight-wire orthodontic treatment. The response rate of the study group was higher than that of the control group (94.00% vs. 72.00%) (P < .05). After 2 years of treatment, PLT, SBI, GI, PD and CAL were decreased in both groups and the observation group was significantly lower than the control group (P < .05). After 6 months of treatment, the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum were decreased in both groups, and the observation group was significantly lower than the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the two groups (P > .05). The treatment of periodontitis without brackets has a significant effect, which can improve the periodontal condition and reduce the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum. Bracketless invisible braces have shown potential clinical significance in improving periodontal indicators and cytokine levels in patients with periodontitis, providing support for providing more comfortable and effective orthodontic treatment options, which may help promote patients' Oral health. These findings suggest the positive role of bracketless invisible braces in comprehensive periodontal treatment, which is expected to influence the practice of orthodontics and periodontal treatment and improve patient treatment experience and effects.

This study investigated the efficacy and safety of a propolis–mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

The aim of this randomized, parallel, controlled clinical trial was to examine the clinical and biochemical efficacy of diode laser as an adjunct to scaling and root planing (SRP). Thirty chronic periodontitis patients were randomly assigned into two groups to receive SRP alone (control) or SRP followed by diode laser (test). Plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment level were measured at baseline and at 1, 3, and 6 months after treatment. The gingival crevicular fluid levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) were analyzed by enzyme-linked immunosorbent assay. Test group showed significantly a better outcome compared to the control group in full-mouth clinical parameters. MMP-1, MMP-8, and TIMP-1 showed significant differences between groups after treatment compared to baseline ( p  < 0.05). The total amount of IL-1β, IL-6, MMP-1, MMP-8, and TIMP-1 decreased ( p  < 0.05) and IL-8 increased after treatment in both test and control groups ( p  < 0.05). Diode laser provided significant improvements in clinical parameters and MMP-8 was significantly impacted by the adjunctive laser treatment at first month providing an insight to how lasers can enhance the outcomes of the nonsurgical periodontal therapy.

This study aimed to investigate the effect of enamel matrix derivatives (EMD) on the early healing biomarkers’ expression following flapless treatment. Thirty-eight patients with residual deep intrabony defects after steps 1 and 2 of periodontal therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Periodontal parameters were recorded at baseline and 6 months after treatment. Gingival crevicular fluid (GCF) was collected at baseline and 2 weeks after treatment to quantify the levels of biomarkers related to epithelial healing (epidermal growth factor, EGF), connective tissue healing (matrix metalloproteinase-8 [MMP-8], fibroblast growth factor [FGF], transforming growth factor-β [TGF-β]), and bone formation (osteoprotegerin [OPG]). The test group showed a significant reduction in MMP-8 levels (p = 0.039), along with significant increases in EGF (p < 0.01), FGF (p < 0.01), and OPG (p < 0.01). The control group demonstrated a significant decrease in MMP-8 (p = 0.010). No significant changes in TGF-β levels were observed in either group. At 6 months, the test group exhibited significantly greater reductions in probing pocket depth and clinical attachment level compared to the control group. This study is the first to characterize the biochemical changes following flapless treatment with EMD. These preliminary findings suggest that EMD may enhance early wound healing by modulating the expression of key regenerative biomarkers.

Background. Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods. Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996–2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results. MPO correlated positively with MMP-8 (rho 0.496, P<0.001) and MMP-9 (rho 0.153, P=0.02) but negatively with TIMP-1 (rho -0.361, P<0.001). MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8–12.9). Conclusions. CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis.

Prolonged angiogenesis inhibition may improve treatment outcome in metastatic colorectal cancer (mCRC) patients. However, due to the complexity of the angiogenic pathways there is a lack of valid predictive biomarkers for anti-angiogenic agents. Here, we describe and optimize a procedure for simultaneous dynamic profiling of multiple angiogenesis related proteins in patient serum to explore associations with the response and acquired resistance to anti-angiogenic therapy. Patients (n=22) were selected from a clinical trial investigating maintenance treatment with bevacizumab alone after response to induction chemotherapy + bevacizumab in mCRC. Serum samples were analysed for 55 unique angiogenesis related proteins using a commercial proteome profiler array and a publicly available image analysis program for quantification. Samples were collected at baseline before induction treatment start, at start of maintenance treatment, and at end of treatment after tumour progression. For eight proteins, the antibody array signals were below detection range in all patient samples. None of the proteins showed levels at baseline or at start of maintenance with strong evidence for correlation to time to progression (lowest nominal p-value 0.03). The dynamic ranges of protein levels measured during the induction treatment period and during the maintenance period were analysed separately for time trends. Evidence for changing trends (up/down) in the levels of MMP-8, TIMP-4 and EGF was observed both during response to induction treatment and at progressive disease, respectively. For three of the proteins (IL-8, Activin A and IGFBP-2), weak evidence for correlation between increasing protein levels during induction with chemotherapy and bevacizumab and time to progression was observed. In conclusion, semi-quantitative profiling of angiogenesis related proteins in patient serum may be a versatile tool to screen for protein patterns aiming at identifying resistance mechanisms of anti-angiogenic treatment in patients with mCRC.

Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L+ and CD80+ pDC. Interestingly, the number of CD80+ pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

Psychosocial stress has profound effects on the body, including the immune system and the brain 1 , 2 . Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD) 3 , the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders. Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.